Regulation of peptide bond cis/trans isomerization by enzyme catalysis and its implication in physiological processes.

In some cases, the slow rotational movement underlying peptide bond cis/trans isomerizations is found to control the biological activity of proteins. Peptide bond cis/trans isomerases as cyclophilins, Fk506-binding proteins, parvulins, and bacterial hsp70 generally assist in the interconversion of the polypeptide substrate cis/trans isomers, and rate acceleration is the dominating mechanism of action in cells. We present evidence disputing the hypothesis that some of the molecular properties of these proteins play an auxiliary role in enzyme function.

[1]  S. Schreiber,et al.  The mechanism of action of cyclosporin A and FK506. , 1992, Immunology today.

[2]  M. Navia,et al.  Protein-drug complexes important for immunoregulation and organ transplantation. , 1996, Current opinion in structural biology.

[3]  R. Abraham,et al.  Isolation of a Protein Target of the FKBP12-Rapamycin Complex in Mammalian Cells (*) , 1995, The Journal of Biological Chemistry.

[4]  G. Fischer,et al.  NMR solution structure of hPar14 reveals similarity to the peptidyl prolyl cis/trans isomerase domain of the mitotic regulator hPin1 but indicates a different functionality of the protein. , 2000, Journal of molecular biology.

[5]  F. Schmid,et al.  Catalysis of protein folding by prolyl isomerase , 1987, Nature.

[6]  T. Silhavy,et al.  Genetic Evidence for Parallel Pathways of Chaperone Activity in the Periplasm of Escherichia coli , 2001, Journal of bacteriology.

[7]  J. Molkentin,et al.  Defective T cell development and function in calcineurin Aβ-deficient mice , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[8]  M. Crompton,et al.  Cyclophilin-A is involved in excitotoxin-induced caspase activation in rat neuronal B50 cells. , 2002, The Biochemical journal.

[9]  P. Halloran,et al.  Immunophilins may limit calcineurin inhibition by cyclosporine and tacrolimus at high drug concentrations. , 2000, Transplantation.

[10]  J. Wells,et al.  Engineering enzyme specificity by "substrate-assisted catalysis". , 1987, Science.

[11]  J. Hacker,et al.  Crystal structure of Mip, a prolylisomerase from Legionella pneumophila , 2001, Nature Structural Biology.

[12]  M. Rapé,et al.  Recognition of protein substrates by the prolyl isomerase trigger factor is independent of proline residues. , 1998, Journal of molecular biology.

[13]  C. Dawson,et al.  Cyclophilin-facilitated bradykinin inactivation in the perfused rat lung. , 1995, Biochemical pharmacology.

[14]  R. Handschumacher,et al.  HIV protease substrate conformation: modulation by cyclophilin A , 1997, FEBS letters.

[15]  D. Kern,et al.  Reassessment of the putative chaperone function of prolyl‐cis/trans‐isomerases , 1994, FEBS letters.

[16]  Xiao Zhen Zhou,et al.  Function of WW domains as phosphoserine- or phosphothreonine-binding modules. , 1999, Science.

[17]  A. E. Counterman,et al.  Cis-trans signatures of proline-containing tryptic peptides in the gas phase. , 2002, Analytical chemistry.

[18]  S. Raina,et al.  A new heat‐shock gene, ppiD, encodes a peptidyl–prolyl isomerase required for folding of outer membrane proteins in Escherichia coli , 1998, The EMBO journal.

[19]  F. Schmid,et al.  Dynamic association of trigger factor with protein substrates. , 2001, Journal of molecular biology.

[20]  R. Nussinov,et al.  Folding and binding cascades: shifts in energy landscapes. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[21]  J. Friedman,et al.  Two cytoplasmic candidates for immunophilin action are revealed by affinity for a new cyclophilin: One in the presence and one in the absence of CsA , 1991, Cell.

[22]  M. Karplus,et al.  Protein Folding: A Perspective from Theory and Experiment. , 1998, Angewandte Chemie.

[23]  H. Yoshikawa,et al.  DnaK Chaperone Machine and Trigger Factor are Only Partially Required for Normal Growth of Bacillus subtilis , 2002, Bioscience, biotechnology, and biochemistry.

[24]  G. Fischer,et al.  The conformation around the peptide bond between the P1- and P2-positions is important for catalytic activity of some proline-specific proteases. , 1983, Biochimica et biophysica acta.

[25]  S. Bartz,et al.  Inhibition of human immunodeficiency virus replication by nonimmunosuppressive analogs of cyclosporin A. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[26]  G Fischer,et al.  Cyclophilin A complexed with a fragment of HIV-1 gag protein: insights into HIV-1 infectious activity. , 1997, Structure.

[27]  H. Bächinger,et al.  Thermal stability and folding of type IV procollagen and effect of peptidyl-prolyl cis-trans-isomerase on the folding of the triple helix. , 1989, The Journal of biological chemistry.

[28]  T. Uchida,et al.  Crosstalk of prolyl isomerases, Pin1/Ess1, and cyclophilin A. , 2001, Biochemical and biophysical research communications.

[29]  J. Kofron,et al.  Continuous fluorimetric direct (uncoupled) assay for peptidyl prolyl cis-trans isomerases , 1992 .

[30]  John J Lemasters,et al.  Inhibition of the mitochondrial permeability transition by the nonimmunosuppressive cyclosporin derivative NIM811. , 2002, Molecular pharmacology.

[31]  P. Halloran,et al.  Calcineurin and the biological effect of cyclosporine and tacrolimus. , 1998, Transplantation proceedings.

[32]  I. Kurek,et al.  Wheat FKBP73 functions in vitro as a molecular chaperone independently of its peptidyl prolyl cis-trans isomerase activity , 2002, Planta.

[33]  Jun O. Liu,et al.  Reversible Inhibition of Calcineurin by the Polyphenolic Aldehyde Gossypol* , 2001, The Journal of Biological Chemistry.

[34]  E. Herman,et al.  The wheat peptidyl prolyl cis-trans-isomerase FKBP77 is heat induced and developmentally regulated. , 1999, Plant physiology.

[35]  B. Bierer,et al.  Identification of Novel Targets of Immunosuppressive Agents by cDNA-based Microarray Analysis* , 2002, The Journal of Biological Chemistry.

[36]  J. Heitman,et al.  The Ess1 prolyl isomerase is linked to chromatin remodeling complexes and the general transcription machinery , 2000, The EMBO journal.

[37]  G. Walker,et al.  Escherichia coli dnaK null mutants are inviable at high temperature , 1987, Journal of bacteriology.

[38]  W. Sundquist,et al.  Molecular recognition in the HIV-1 capsid/cyclophilin A complex. , 1997, Journal of molecular biology.

[39]  P. Baine.  Comparison of rate constants determined by two‐dimensional NMR spectroscopy with rate constants determined by other NMR techniques , 1986 .

[40]  F. Schmid,et al.  Kinetic models for unfolding and refolding of ribonuclease T1 with substitution of cis-proline 39 by alanine. , 1993, Journal of molecular biology.

[41]  N. Sigal,et al.  Is cyclophilin involved in the immunosuppressive and nephrotoxic mechanism of action of cyclosporin A? , 1991, The Journal of experimental medicine.

[42]  M. Choder,et al.  Rapamycin Blocks Sexual Development in Fission Yeast through Inhibition of the Cellular Function of an FKBP12 Homolog* , 2001, The Journal of Biological Chemistry.

[43]  H. Halvorson,et al.  Consideration of the Possibility that the slow step in protein denaturation reactions is due to cis-trans isomerism of proline residues. , 1975, Biochemistry.

[44]  P. Halloran,et al.  Evidence that calcineurin is rate-limiting for primary human lymphocyte activation. , 1997, The Journal of clinical investigation.

[45]  J. Massagué,et al.  Mechanism of TGFβ receptor inhibition by FKBP12 , 1997, The EMBO journal.

[46]  Ya-Li Yao,et al.  The FK506‐binding protein 25 functionally associates with histone deacetylases and with transcription factor YY1 , 2001, The EMBO journal.

[47]  A. Goldberg,et al.  Involvement of the chaperonin dnaK in the rapid degradation of a mutant protein in Escherichia coli. , 1992, The EMBO journal.

[48]  C. Yan,et al.  Cyclophilin A is a secreted growth factor induced by oxidative stress. , 2000, Circulation research.

[49]  D. Kern,et al.  The cis/trans interconversion of the calcium regulating hormone calcitonin is catalyzed by cyclophilin , 1993, FEBS letters.

[50]  K Dolinski,et al.  All cyclophilins and FK506 binding proteins are, individually and collectively, dispensable for viability in Saccharomyces cerevisiae. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[51]  G. Binsch.  Unified theory of exchange effects on nuclear magnetic resonance line shapes , 1969 .

[52]  M. Bukrinsky,et al.  CD147 facilitates HIV-1 infection by interacting with virus-associated cyclophilin A , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[53]  J. Buchner,et al.  Localization of the Chaperone Domain of FKBP52* , 2001, The Journal of Biological Chemistry.

[54]  E. A. O'neill,et al.  T cell responses in calcineurin A alpha-deficient mice , 1996, The Journal of experimental medicine.

[55]  U. Reimer,et al.  Substrate-based design of reversible Pin1 inhibitors. , 2002, Biochemistry.

[56]  J. Luban,et al.  Inhibition of HIV-1 replication by cyclosporine A or related compounds correlates with the ability to disrupt the Gag-cyclophilin A interaction. , 1996, Virology.

[57]  T. Hunter,et al.  Loss of Pin1 function in the mouse causes phenotypes resembling cyclin D1-null phenotypes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[58]  B. Ryffel,et al.  The side-effects of ciclosporine-A and tacrolimus. , 1998, Clinical nephrology.

[59]  FKB1 encodes a nonessential FK 506-binding protein in Saccharomyces cerevisiae and contains regions suggesting homology to the cyclophilins. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[60]  N. Colley,et al.  Role of Asparagine-linked Oligosaccharides in Rhodopsin Maturation and Association with Its Molecular Chaperone, NinaA* , 2000, The Journal of Biological Chemistry.

[61]  M. Bukrinsky,et al.  Active Site Residues of Cyclophilin A Are Crucial for Its Signaling Activity via CD147* , 2002, The Journal of Biological Chemistry.

[62]  C. Clevenger,et al.  The intranuclear prolactin/cyclophilin B complex as a transcriptional inducer , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[63]  C. Morris,et al.  A novel human gene FKBP6 is deleted in Williams syndrome. , 1998, Genomics.

[64]  Stuart K. Calderwood,et al.  HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine , 2000, Nature Medicine.

[65]  J. Buchner,et al.  Chaperone Function of Hsp90-Associated Proteins , 1996, Science.

[66]  J. Heitman,et al.  Two cyclophilin A homologs with shared and distinct functions important for growth and virulence of Cryptococcus neoformans , 2001, EMBO reports.

[67]  T. Hsu,et al.  Drosophila Pin1 prolyl isomerase Dodo is a MAP kinase signal responder during oogenesis , 2001, Nature Cell Biology.

[68]  K. Hellingwerf,et al.  A gene of Acinetobacter calcoaceticus BD413 encodes a periplasmic peptidyl-prolyl cis-trans isomerase of the cyclophilin sub-class that is not essential for growth. , 1994, Biochimica et biophysica acta.

[69]  B. Bukau,et al.  Role of the DnaK and HscA homologs of Hsp70 chaperones in protein folding in E.coli , 1998, The EMBO journal.

[70]  F. Schmid,et al.  Non-prolyl cis-trans peptide bond isomerization as a rate-determining step in protein unfolding and refolding. , 1995, Journal of molecular biology.

[71]  Hwa-Young Kim,et al.  Crystal structure of calcineurin–cyclophilin–cyclosporin shows common but distinct recognition of immunophilin–drug complexes , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[72]  M. Matzuk,et al.  Cardiac defects and altered ryanodine receptor function in mice lacking FKBP12 , 1998, Nature.

[73]  D. Mckay,et al.  Crystallographic structure of SurA, a molecular chaperone that facilitates folding of outer membrane porins. , 2002, Structure.

[74]  Time-resolved FTIR difference spectroscopy as tool for investigating refolding reactions of ribonuclease T1 synchronized with trans --> cis prolyl isomerization. , 2002, Biopolymers.

[75]  K. Young,et al.  Escherichia coli and other species of the enterobacteriaceae encode a protein similar to the family of Mip-like FK506-binding proteins , 1995, Archives of Microbiology.

[76]  C. Green,et al.  Cyclophilins are induced by hypoxia and heat stress in myogenic cells. , 1997, Biochemical and biophysical research communications.

[77]  S. Hanes,et al.  The Ess1 prolyl isomerase is required for growth and morphogenetic switching in Candida albicans. , 2002, Genetics.

[78]  S. Forsén,et al.  Peptidyl‐prolyl cis‐trans isomerase activity as studied by dynamic proton NMR spectroscopy , 1991, FEBS letters.

[79]  T. Schindler,et al.  Prolyl isomerases do not catalyze isomerization of non-prolyl peptide bonds. , 1998, Biological chemistry.

[80]  U. Hahn,et al.  Folding of ribonuclease T1. 1. Existence of multiple unfolded states created by proline isomerization. , 1990, Biochemistry.

[81]  C. Dobson,et al.  Development of Enzymatic Activity during Protein Folding , 1999, The Journal of Biological Chemistry.

[82]  K. Chow,et al.  Overexpression of dnaK/dnaJ and groEL confers freeze tolerance to Escherichia coli. , 1998, Biochemical and biophysical research communications.

[83]  A. Schnapp,et al.  Phosphorylation-dependent proline isomerization catalyzed by Pin1 is essential for tumor cell survival and entry into mitosis. , 2000, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[84]  C. Pace,et al.  Conformational stability and mechanism of folding of ribonuclease T1. , 1989, The Journal of biological chemistry.

[85]  P. Frendo,et al.  Effects of abiotic stresses on cyclophilin gene expression in maize and bean and sequence analysis of bean cyclophilin cDNA , 1992 .

[86]  G. Fischer,et al.  Evaluation of Similarities in the cis/trans Isomerase Function of Trigger Factor and DnaK , 2002, Biological chemistry.

[87]  C. Vanpouille,et al.  Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[88]  D. A. Bosco,et al.  Catalysis of cis/trans isomerization in native HIV-1 capsid by human cyclophilin A , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[89]  J J Burbaum,et al.  Evolutionary optimization of the catalytic effectiveness of an enzyme. , 1989, Biochemistry.

[90]  P. Caspers,et al.  Cyclophilin-promoted folding of mouse dihydrofolate reductase does not include the slow conversion of the late-folding intermediate to the active enzyme. , 2000, Journal of molecular biology.

[91]  J. Kofron,et al.  A continuous spectrophotometric direct assay for peptidyl prolyl cis-trans isomerases. , 1993, Biochemical and biophysical research communications.

[92]  J. Luban.  Absconding with the Chaperone: Essential Cyclophilin–Gag Interaction in HIV-1 Virions , 1996, Cell.

[93]  J. Betton,et al.  Chaperone function of FkpA, a heat shock prolyl isomerase, in the periplasm of Escherichia coli , 2001, Molecular microbiology.

[94]  M. Schutkowski,et al.  Evidence that the substrate backbone conformation is critical to phosphorylation by p42 MAP kinase , 2000, FEBS letters.

[95]  S. Harrison,et al.  Crystal structure of human calcineurin complexed with cyclosporin A and human cyclophilin , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[96]  A. Plückthun,et al.  The Periplasmic Escherichia coli Peptidylprolyl cis,trans-Isomerase FkpA , 2000, The Journal of Biological Chemistry.

[97]  S. Ness,et al.  Point mutations in v-Myb disrupt a cyclophilin-catalyzed negative regulatory mechanism. , 1998, Molecular cell.

[98]  J. Heitman,et al.  FKBP12 is not required for the modulation of transforming growth factor beta receptor I signaling activity in embryonic fibroblasts and thymocytes. , 1998, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[99]  J. Luban,et al.  Cyclophilin A Peptidyl-Prolyl Isomerase Activity Promotes Zpr1 Nuclear Export , 2002, Molecular and Cellular Biology.

[100]  R. Morimoto,et al.  Molecular Chaperone Machines: Chaperone Activities of the Cyclophilin Cyp-40 and the Steroid Aporeceptor-Associated Protein p23 , 1996, Science.

[101]  S. Snyder,et al.  FKBP12, the 12-kDa FK506-binding protein, is a physiologic regulator of the cell cycle , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[102]  M. Kobayashi,et al.  Distinct tissue and cellular distribution of two major isoforms of calcineurin. , 1997, Molecular immunology.

[103]  M. Caparon,et al.  A role for Trigger Factor and an Rgg‐like regulator in the transcription, secretion and processing of the cysteine proteinase of Streptococcus pyogenes , 1998, The EMBO journal.

[104]  S. Schreiber,et al.  Synthesis and analysis of 506BD, a high-affinity ligand for the immunophilin FKBP , 1991 .

[105]  G. Fischer,et al.  Conformational specificity of chymotrypsin toward proline-containing substrates. , 1984, Biochimica et biophysica acta.

[106]  J. Heitman,et al.  Molecular cloning and characterization of Aspergillus nidulans cyclophilin B. , 1999, Fungal genetics and biology : FG & B.

[107]  G. Fischer,et al.  FKBP ligands as novel therapeutics for neurological disorders. , 2001, Mini reviews in medicinal chemistry.

[108]  J. Frydman.  Folding of newly translated proteins in vivo: the role of molecular chaperones. , 2001, Annual review of biochemistry.

[109]  F. Hartl,et al.  Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding , 1992, Nature.

[110]  U. Reimer,et al.  Mapping the stereospecificity of peptidyl prolyl cis/trans isomerases , 1998, FEBS letters.

[111]  G. L. Miklos,et al.  The Drosophila melanogaster dodo (dod) gene, conserved in humans, is functionally interchangeable with the ESS1 cell division gene of Saccharomyces cerevisiae. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[112]  G. Fischer,et al.  FKBP‐like catalysis of peptidyl‐prolyl bond isomerization by micelles and membranes , 1997 .

[113]  M. Sarvas,et al.  The PrsA lipoprotein is essential for protein secretion in Bacillus subtilis and sets a limit for high‐level secretion , 1993, Molecular microbiology.

[114]  J. Luban,et al.  Isolation, characterization and targeted disruption of mouse ppia: cyclophilin A is not essential for mammalian cell viability. , 2000, Genomics.

[115]  P. Halloran,et al.  Quantitating immunosuppression. Estimating the 50% inhibitory concentration for in vivo cyclosporine in mice. , 1996, Transplantation.

[116]  B. Bukau,et al.  Trigger factor and DnaK cooperate in folding of newly synthesized proteins , 1999, Nature.

[117]  W. Ou,et al.  Chaperone‐like activity of peptidyl‐prolyl cis‐trans isomerase during creatine kinase refolding , 2001, Protein science : a publication of the Protein Society.

[118]  R. Ranganathan,et al.  Structural and Functional Analysis of the Mitotic Rotamase Pin1 Suggests Substrate Recognition Is Phosphorylation Dependent , 1997, Cell.

[119]  C. Frömmel,et al.  Novel disulfide‐constrained pentapeptides as models for β‐VIa turns in proteins , 1995 .

[120]  G. Crabtree,et al.  Calcineurin inhibitors and the generalization of the presenting protein strategy. , 2001, Advances in protein chemistry.

[121]  M. Marahiel,et al.  Cyclophilin and trigger factor from Bacillus subtilis catalyze in vitro protein folding and are necessary for viability under starvation conditions. , 1998, Biochemistry.

[122]  F. Hartl,et al.  Polypeptide Flux through Bacterial Hsp70 DnaK Cooperates with Trigger Factor in Chaperoning Nascent Chains , 1999, Cell.

[123]  S. Forsburg,et al.  Isolation and characterization of the Pin1/Ess1p homologue in Schizosaccharomyces pombe. , 2001, Journal of cell science.

[124]  Separation of cis/trans isomers of a prolyl peptide bond by capillary zone electrophoresis , 1994, Electrophoresis.

[125]  V. Bindokas,et al.  The role of immunophilins in mutant superoxide dismutase-1linked familial amyotrophic lateral sclerosis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[126]  F. Schmid.  Fast-folding and slow-folding forms of unfolded proteins. , 1986, Methods in enzymology.

[127]  F. Schmid,et al.  Kinetic analysis of the unfolding and refolding of ribonuclease T1 by a stopped-flow double-mixing technique. , 1996, Biochemistry.

[128]  J. Micol,et al.  Mutations in the ULTRACURVATA2 gene of Arabidopsis thaliana, which encodes a FKBP-like protein, cause dwarfism, leaf epinasty and helical rotation of several organs , 2001 .

[129]  A. Halestrap,et al.  Sanglifehrin A Acts as a Potent Inhibitor of the Mitochondrial Permeability Transition and Reperfusion Injury of the Heart by Binding to Cyclophilin-D at a Different Site from Cyclosporin A* , 2002, The Journal of Biological Chemistry.

[130]  M. J. Kennedy,et al.  Identification of Actinobacillus pleuropneumoniae virulence genes using signature-tagged mutagenesis in a swine infection model. , 2000, Microbial pathogenesis.

[131]  J. Sambrook,et al.  Proline isomerases function during heat shock. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[132]  J. Heitman,et al.  Cyclophilin A and Ess1 interact with and regulate silencing by the Sin3–Rpd3 histone deacetylase , 2000, The EMBO journal.

[133]  S. Schreiber,et al.  Rapamycin-modulated transcription defines the subset of nutrient-sensitive signaling pathways directly controlled by the Tor proteins. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[134]  J. Schneider-Mergener,et al.  Binding specificity of Escherichia coli trigger factor , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[135]  N. Cianciotto,et al.  Legionella pneumophila mip gene potentiates intracellular infection of protozoa and human macrophages. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[136]  H. Bächinger.  The influence of peptidyl-prolyl cis-trans isomerase on the in vitro folding of type III collagen. , 1987, The Journal of biological chemistry.

[137]  T. Bernhardt,et al.  The Escherichia coli FKBP‐type PPIase SlyD is required for the stabilization of the E lysis protein of bacteriophage φX174 , 2002, Molecular microbiology.

[138]  J. Rahfeld,et al.  Characterization of Arabidopsis thaliana AtFKBP42 that is membrane-bound and interacts with Hsp90. , 2002, The Plant journal : for cell and molecular biology.

[139]  Stuart L. Schreiber,et al.  A mammalian protein targeted by G1-arresting rapamycin–receptor complex , 1994, Nature.

[140]  M. Caboche,et al.  Mutation in the Arabidopsis PASTICCINO1Gene, Which Encodes a New FK506-Binding Protein-Like Protein, Has a Dramatic Effect on Plant Development , 1998, Molecular and Cellular Biology.

[141]  U. Hahn,et al.  Folding of ribonuclease T1. 2. Kinetic models for the folding and unfolding reactions. , 1990, Biochemistry.

[142]  M. Kirschner,et al.  Sequence-specific and phosphorylation-dependent proline isomerization: a potential mitotic regulatory mechanism. , 1997, Science.

[143]  M. Kleerebezem,et al.  Characterization of an Escherichia coli rotA mutant, affected in periplasmic peptidyl‐prolyl cis/trans isomerase , 1995, Molecular microbiology.

[144]  G. Wilson,et al.  A novel human stress response-related gene with a potential role in induced radioresistance. , 1999, Radiation research.

[145]  T. Schindler,et al.  A protein folding intermediate of ribonuclease T1 characterized at high resolution by 1D and 2D real-time NMR spectroscopy. , 1999, Journal of molecular biology.

[146]  J. Brandts,et al.  Isomer-specific proteolysis of model substrates: influence that the location of the proline residue exerts on cis/trans specificity. , 1985, Biochemistry.

[147]  W. Sundquist,et al.  Crystal Structure of Human Cyclophilin A Bound to the Amino-Terminal Domain of HIV-1 Capsid , 1996, Cell.

[148]  P. Gallay,et al.  trans-Complementation Rescue of Cyclophilin A-Deficient Viruses Reveals that the Requirement for Cyclophilin A in Human Immunodeficiency Virus Type 1 Replication Is Independent of Its Isomerase Activity , 2002, Journal of Virology.

[149]  S. Snyder,et al.  Neurotrophic actions of nonimmunosuppressive analogues of immunosuppressive drugs FK506, rapamycin and cyclosporin A , 1997, Nature Medicine.

[150]  Weiqin Zhao,et al.  Peptidyl‐prolyl‐cis/trans‐isomerase activity may be necessary for memory formation , 1998, FEBS letters.

[151]  Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay. , 1991 .

[152]  P. Shaw.  Peptidyl‐prolyl isomerases: a new twist to transcription , 2002, EMBO reports.

[153]  D. G. Davis,et al.  Bradykinin and its Gly6 analogue are substrates of cyclophilin: a fluorine-19 magnetization transfer study. , 1990, Biochemistry.

[154]  M. Schutkowski,et al.  Inhibition of peptidyl-prolyl cis/trans isomerase activity by substrate analog structures: thioxo tetrapeptide-4-nitroanilides. , 1995, Biochemistry.

[155]  R. Wetzker,et al.  Effects of FK506-binding Protein 12 and FK506 on Autophosphorylation of Epidermal Growth Factor Receptor* , 1998, The Journal of Biological Chemistry.

[156]  A. Kaplan,et al.  A Cyanobacterial Gene Encoding Peptidyl-Prolyl cis-trans Isomerase. , 1992, Plant physiology.

[157]  J. Hacker,et al.  Influence of site specifically altered Mip proteins on intracellular survival of Legionella pneumophila in eukaryotic cells , 1995, Infection and immunity.

[158]  S. Rüdiger,et al.  Functional Dissection of Trigger Factor and DnaK: Interactions with Nascent Polypeptides and Thermally Denatured Proteins , 2001, Biological chemistry.

[159]  T. Maruyama,et al.  FK506 binding protein from a thermophilic archaeon, Methanococcus thermolithotrophicus, has chaperone-like activity in vitro. , 2000, Biochemistry.

[160]  U. Reimer,et al.  Extended binding sites of cyclophilin as revealed by the interaction with HIV‐1 Gag polyprotein derived oligopeptides , 1996, FEBS letters.

[161]  S. Gottesman,et al.  Substrate sequestration by a proteolytically inactive Lon mutant. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[162]  V. Rybin,et al.  Crystal structure of the protein disulfide bond isomerase, DsbC, from Escherichia coli , 2000, Nature Structural Biology.

[163]  A. Andreotti,et al.  Structural characterization of a proline-driven conformational switch within the Itk SH2 domain , 2002, Nature Structural Biology.

[164]  M. Bukrinsky.  Cyclophilins: unexpected messengers in intercellular communications. , 2002, Trends in immunology.

[165]  D. Lawrence,et al.  Role of the Catalytic Serine in the Interactions of Serine Proteinases with Protein Inhibitors of the Serpin Family , 1995, The Journal of Biological Chemistry.

[166]  C. Schiene‐Fischer,et al.  Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases , 2001, FEBS letters.

[167]  R. Kolter,et al.  surA, an Escherichia coli gene essential for survival in stationary phase , 1990, Journal of bacteriology.

[168]  M. Bukrinsky,et al.  CD147 is a signaling receptor for cyclophilin B. , 2001, Biochemical and biophysical research communications.

[169]  A. Oberhauser,et al.  Multiple conformations of PEVK proteins detected by single-molecule techniques , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[170]  C. Clevenger,et al.  Role of cyclophilin B in prolactin signal transduction and nuclear retrotranslocation. , 2000, Molecular endocrinology.

[171]  K. Young,et al.  Decreased intracellular survival of an fkpA mutant of Salmonella typhimurium Copenhagen , 1997, Infection and immunity.

[172]  H. Domdey,et al.  PTF1 encodes an essential protein in Saccharomyces cerevisiae, which shows strong homology with a new putative family of PPIases , 1995, FEBS letters.

[173]  J. Cidlowski,et al.  A calcium-dependent nuclease from apoptotic rat thymocytes is homologous with cyclophilin. Recombinant cyclophilins A, B, and C have nuclease activity. , 1994, The Journal of biological chemistry.

[174]  K. Wüthrich,et al.  A novel approach for studies of the molecular conformations in flexible polypeptides , 1974, FEBS letters.

[175]  I. Campbell,et al.  Effects of proline cis‐trans isomerization on TB domain secondary structure , 1998, Protein science : a publication of the Protein Society.

[176]  Mark A. Magnuson,et al.  Oestrogen protects FKBP12.6 null mice from cardiac hypertrophy , 2002, Nature.

[177]  G. Fischer,et al.  The mode of action of peptidyl prolyl cis/trans isomerases in vivo: binding vs. catalysis , 1998, FEBS letters.

[178]  C. Lyttle,et al.  Leukocyte chemotactic activity of FKBP and inhibition by FK506. , 1992, Biochemical and biophysical research communications.

[179]  J. Hacker,et al.  A cyclophilin‐like peptidyl‐prolyl cis/trans isomerase from Legionella pneumophila – characterization, molecular cloning and overexpression , 1996, Molecular microbiology.

[180]  L. Zhu,et al.  The chaperone activity of trigger factor is distinct from its isomerase activity during co‐expression with adenylate kinase in Escherichia coli , 2001, FEBS letters.

[181]  G Fischer,et al.  Direct measurement indicates a slow cis/trans isomerization at the secondary amide peptide bond of glycylglycine. , 2001, Journal of the American Chemical Society.

[182]  S. Macedo-Ribeiro,et al.  Trypanosoma cruzi macrophage infectivity potentiator has a rotamase core and a highly exposed α‐helix , 2002, EMBO reports.

[183]  M. Zurini,et al.  Sanglifehrin A, a Novel Cyclophilin-Binding Compound Showing Immunosuppressive Activity with a New Mechanism of Action , 2001, The Journal of Immunology.

[184]  Ulf Reimer,et al.  Barriers to Rotation of Secondary Amide Peptide Bonds , 1998 .

[185]  Truffa-Bachi,et al.  Proteomic analysis of T cell activation in the presence of cyclosporin A: immunosuppressor and activator removal induces de novo protein synthesis. , 2000, Molecular immunology.

[186]  V. Hsu,et al.  Peptidyl-prolyl cis-trans isomerase activity of cyclophilin studied by one-dimensional proton nuclear magnetic resonance spectroscopy , 1990 .

[187]  M. Marahiel,et al.  Cloning and characterization of ppiB, a Bacillus subtilis gene which encodes a cyclosporine A‐sensitive peptidyl‐prolyl cis‐trans isomerase , 1994, Molecular microbiology.

[188]  J. Brandts,et al.  Catalysis of proline isomerization during protein-folding reactions. , 1988, Biochimica et biophysica acta.

[189]  M. Schutkowski,et al.  A protease-free assay for peptidyl prolyl cis/trans isomerases using standard peptide substrates. , 1997, Analytical biochemistry.

[190]  H. Dyson,et al.  Stabilization of a type VI turn in a family of linear peptides in water solution. , 1994, Journal of molecular biology.

[191]  A. Means,et al.  Requirement of the prolyl isomerase Pin1 for the replication checkpoint. , 2000, Science.

[192]  W. Wickner,et al.  Trigger factor depletion or overproduction causes defective cell division but does not block protein export , 1990, Journal of bacteriology.

[193]  J. Enghild,et al.  Complexes between serpins and inactive proteinases are not thermodynamically stable but are recognized by serpin receptors. , 1994, Journal of Biological Chemistry.

[194]  C. Bellini,et al.  FKBPs: at the crossroads of folding and transduction. , 2001, Trends in plant science.

[195]  M. Schreier,et al.  Inhibition of T-cell signaling pathways by immunophilin drug complexes: are side effects inherent to immunosuppressive properties? , 1993, Transplantation proceedings.

[196]  C. Uchida,et al.  Mice lacking Pin1 develop normally, but are defective in entering cell cycle from G(0) arrest. , 1999, Biochemical and biophysical research communications.

[197]  P. Halloran,et al.  Calcineurin activity is only partially inhibited in leukocytes of cyclosporine-treated patients. , 1995, Transplantation.

[198]  G. Fischer,et al.  Separation of cis/trans conformers of human and salmon calcitonin by low temperature capillary electrophoresis , 1998, Electrophoresis.

[199]  M. Kirschner,et al.  Pin1 acts catalytically to promote a conformational change in Cdc25. , 2001, Molecular cell.

[200]  W. Campbell,et al.  Role of FKBP12.6 in cADPR-induced activation of reconstituted ryanodine receptors from arterial smooth muscle. , 2002, American journal of physiology. Heart and circulatory physiology.

[201]  P. Caron,et al.  X-ray structure of calcineurin inhibited by the immunophilin-immunosuppressant FKBP12-FK506 complex , 1995, Cell.

[202]  Ulf Reimer,et al.  Nonprolyl cis peptide bonds in unfolded proteins cause complex folding kinetics , 2001, Nature Structural Biology.

[203]  A. Halestrap,et al.  The permeability transition pore complex: another view. , 2002, Biochimie.

[204]  G Fischer,et al.  Pin1-dependent prolyl isomerization regulates dephosphorylation of Cdc25C and tau proteins. , 2000, Molecular cell.

[205]  D. Missiakas,et al.  Characterization of the Escherichia coliςE Regulon* , 2001, The Journal of Biological Chemistry.

[206]  M. Ehrmann,et al.  A Temperature-Dependent Switch from Chaperone to Protease in a Widely Conserved Heat Shock Protein , 1999, Cell.

[207]  J. Heitman,et al.  FK 506-binding protein proline rotamase is a target for the immunosuppressive agent FK 506 in Saccharomyces cerevisiae. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[208]  F. Schmid,et al.  Generation of a non-prolyl cis peptide bond in ribonuclease T1. , 1994, Journal of molecular biology.

[209]  Ulf Reimer,et al.  Local structural changes caused by peptidyl-prolyl cis/trans isomerization in the native state of proteins. , 2002, Biophysical chemistry.

[210]  G Fischer,et al.  Side-chain effects on peptidyl-prolyl cis/trans isomerisation. , 1998, Journal of molecular biology.

[211]  G. Dougan,et al.  Salmonella enterica Serovar TyphimuriumsurA Mutants Are Attenuated and Effective Live Oral Vaccines , 2000, Infection and Immunity.

[212]  D. Kern,et al.  Kinetic analysis of cyclophilin-catalyzed prolyl cis/trans isomerization by dynamic NMR spectroscopy. , 1995, Biochemistry.

[213]  J. Hiscott,et al.  Posttranslational regulation of IRF-4 activity by the immunophilin FKBP52. , 2000, Immunity.

[214]  G. Richarme,et al.  Interaction of DnaK with native proteins and membrane proteins correlates with their accessible hydrophobicity. , 1999, Gene.

[215]  J. Brandts,et al.  Evidence suggesting that some proteolytic enzymes may cleave only the trans form of the peptide bond. , 1979, Biochemistry.

[216]  T. Kiefhaber,et al.  Cyclophilin and peptidyl-prolyl cis-trans isomerase are probably identical proteins , 1989, Nature.

[217]  B. Haendler,et al.  Receptor type I and type II binding regions and the peptidyl-prolyl isomerase site of cyclophilin B are required for enhancement of T-lymphocyte adhesion to fibronectin. , 2002, Biochemistry.

[218]  Stuart L. Schreiber,et al.  Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes , 1991, Cell.

[219]  A. Plückthun,et al.  High enzymatic activity and chaperone function are mechanistically related features of the dimeric E. coli peptidyl-prolyl-isomerase FkpA. , 2001, Journal of molecular biology.

[220]  D. Quinn,et al.  Cloning and characterization of two immunophilin-like genes, ilpA and fkpA, on a single 3.9-kilobase fragment of Aeromonas hydrophila genomic DNA , 1997, Journal of bacteriology.

[221]  Y. Liou,et al.  Pinning down proline-directed phosphorylation signaling. , 2002, Trends in cell biology.

[222]  J. Luban,et al.  Cyclophilin A regulates HIV‐1 infectivity, as demonstrated by gene targeting in human T cells , 2001, The EMBO journal.

[223]  J. Bartlett,et al.  Activation and regulation of interferon regulatory factor 4 in HTLV type 1-infected T lymphocytes. , 2000, AIDS research and human retroviruses.

[224]  C. Dawson,et al.  Angiotensin-converting enzyme preferentially hydrolyzes trans isomer of proline-containing substrate. , 1993, Journal of applied physiology.

[225]  K. Young,et al.  slyD, a host gene required for phi X174 lysis, is related to the FK506-binding protein family of peptidyl-prolyl cis-trans-isomerases. , 1994, The Journal of biological chemistry.

[226]  G. Fischer,et al.  Semiautomated microtiter plate assay for monitoring peptidylprolyl cis/trans isomerase activity in normal and pathological human sera. , 1998, Clinical chemistry.

[227]  C. Lyttle,et al.  Leukocyte chemotactic activity of cyclophilin. , 1992, The Journal of biological chemistry.

[228]  J. Thornton,et al.  Influence of proline residues on protein conformation. , 1991, Journal of molecular biology.

[229]  A. Goldberg,et al.  Trigger factor is induced upon cold shock and enhances viability of Escherichia coli at low temperatures. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[230]  R. London,et al.  Conformational Selectivity of HIV-1 Protease Cleavage of X-Pro Peptide Bonds and Its Implications* , 1997, The Journal of Biological Chemistry.

[231]  Morgan Huse,et al.  Crystal Structure of the Cytoplasmic Domain of the Type I TGF β Receptor in Complex with FKBP12 , 1999, Cell.

[232]  Da-Ting Lin,et al.  Mitochondrial Targeted Cyclophilin D Protects Cells from Cell Death by Peptidyl Prolyl Isomerization* , 2002, The Journal of Biological Chemistry.

[233]  G. Fischer,et al.  Peptidyl-prolyl cis/trans isomerases and their effectors , 1994 .

[234]  F. Schmid,et al.  Cooperation of enzymatic and chaperone functions of trigger factor in the catalysis of protein folding , 1997, The EMBO journal.

[235]  I. Barthelmess,et al.  FK506-binding protein of Neurospora crassa (NcFKBP) mediates sensitivity to the immunosuppressant FK506; resistant mutants identify two loci , 2004, Current Genetics.

[236]  C. Dobson,et al.  A magnetization-transfer nuclear magnetic resonance study of the folding of staphylococcal nuclease. , 1989, Biochemistry.

[237]  V. Hsu,et al.  Thermodynamics of cyclophilin catalyzed peptidyl‐prolyl isomerization by nmr spectroscopy , 1994, Biopolymers.

[238]  L. Ruddock,et al.  Interaction of the periplasmic peptidylprolyl cis-trans isomerase SurA with model peptides. The N-terminal region of SurA id essential and sufficient for peptide binding. , 2001, The Journal of biological chemistry.

[239]  C. Gross,et al.  The SurA periplasmic PPIase lacking its parvulin domains functions in vivo and has chaperone activity , 2001, The EMBO journal.

[240]  F. Schmid,et al.  The hsp70 chaperone DnaK is a secondary amide peptide bond cis-trans isomerase , 2002, Nature Structural Biology.

[241]  F. Schmid,et al.  Enzymatic catalysis of prolyl isomerization in an unfolding protein. , 1992, Biochemistry.