Structures of proteins of biomedical interest from the Center for Eukaryotic Structural Genomics

The Center for Eukaryotic Structural Genomics (CESG) produces and solves the structures of proteins from eukaryotes. We have developed and operate a pipeline to both solve structures and to test new methodologies. Both NMR and X-ray crystallography methods are used for structure solution. CESG chooses targets based on sequence dissimilarity to known structures, medical relevance, and nominations from members of the scientific community. Many times proteins qualify in more than one of these categories. Here we review some of the structures that have connections to human health and disease.

[1]  T. Ørntoft,et al.  Secretagogin Is a Novel Marker for Neuroendocrine Differentiation , 2006, Neuroendocrinology.

[2]  G. D'alessio,et al.  A dimeric mutant of human pancreatic ribonuclease with selective cytotoxicity toward malignant cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[3]  B. Nidetzky,et al.  Variations of the 2‐His‐1‐carboxylate Theme in Mononuclear Non‐Heme FeII Oxygenases , 2006, Chembiochem : a European journal of chemical biology.

[4]  J. Jaeken,et al.  The carbohydrate-deficient glycoprotein syndrome. A new inherited multisystemic disease with severe nervous system involvement. , 1991, Acta paediatrica Scandinavica. Supplement.

[5]  M. Seno,et al.  Inhibition of cell growth by a fused protein of human ribonuclease 1 and human basic fibroblast growth factor. , 1999, Protein engineering.

[6]  D. Krasnewich,et al.  A deletion-insertion mutation in the phosphomannomutase 2 gene in an African American patient with congenital disorders of glycosylation-Ia. , 2002, American journal of medical genetics.

[7]  G. D'alessio,et al.  Ribonuclease A can be transformed into a dimeric ribonuclease with antitumor activity. , 1994, The Journal of biological chemistry.

[8]  M. Schwartz,et al.  Carbohydrate-deficient glycoprotein syndrome type 1A: expression and characterisation of wild type and mutant PMM2 in E. coli , 1999, European Journal of Human Genetics.

[9]  K. M. Mulder,et al.  A novel transforming growth factor-beta receptor-interacting protein that is also a light chain of the motor protein dynein. , 2002, Molecular biology of the cell.

[10]  Lawrence Que,et al.  The 2-His-1-carboxylate facial triad: a versatile platform for dioxygen activation by mononuclear non-heme iron(II) enzymes , 2005, JBIC Journal of Biological Inorganic Chemistry.

[11]  J. Coyle,et al.  N-Acetylaspartate in neuropsychiatric disorders , 1995, Progress in Neurobiology.

[12]  M. McPherson,et al.  Novel thioether bond revealed by a 1.7 Å crystal structure of galactose oxidase , 1994, Nature.

[13]  E. Schaftingen,et al.  Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A. , 1998, American journal of human genetics.

[14]  M. Stipanuk,et al.  Evaluation and modification of an assay procedure for cysteine dioxygenase activity: high-performance liquid chromatography method for measurement of cysteine sulfinate and demonstration of physiological relevance of cysteine dioxygenase activity in cysteine catabolism. , 1995, Analytical biochemistry.

[15]  R. Viola,et al.  Characterization of Human Aspartoacylase: the brain enzyme responsible for Canavan disease , 2006, Biochemistry.

[16]  R. Gill,et al.  Proteomics as a tool for discovery: proteins implicated in Alzheimer's disease are highly expressed in normal pancreatic islets. , 2003, Journal of proteome research.

[17]  R. Matalon.  Canavan disease: diagnosis and molecular analysis. , 1997, Genetic testing.

[18]  W. Valentine,et al.  Characteristics of a pyrimidine-specific 5'-nucleotidase in human erythrocytes. , 1975, The Journal of biological chemistry.

[19]  Paolo Gasparini,et al.  Ethylmalonic encephalopathy is caused by mutations in ETHE1, a gene encoding a mitochondrial matrix protein. , 2004, American journal of human genetics.

[20]  Ronald T Raines,et al.  Inhibition of human pancreatic ribonuclease by the human ribonuclease inhibitor protein. , 2005, Journal of molecular biology.

[21]  G. Matthijs,et al.  Phosphomannomutase deficiency: the molecular basis of the classical Jaeken syndrome (CDGS type Ia). , 1999, Molecular genetics and metabolism.

[22]  R. Raines,et al.  Contribution of active-site residues to the function of onconase, a ribonuclease with antitumoral activity. , 2003, Biochemistry.

[23]  G. Phillips,et al.  Structure of Pyrimidine 5′-Nucleotidase Type 1 , 2006, Journal of Biological Chemistry.

[24]  E. Bertini,et al.  New clinical phenotype of branched-chain acyl-CoA oxidation defect , 1991, The Lancet.

[25]  G. Phillips,et al.  Comparison of cell‐based and cell‐free protocols for producing target proteins from the Arabidopsis thaliana genome for structural studies , 2005, Proteins.

[26]  I. Milisav.  Dynein and dynein-related genes. , 1998, Cell motility and the cytoskeleton.

[27]  George N. Phillips,et al.  Structure of aspartoacylase, the brain enzyme impaired in Canavan disease , 2007, Proceedings of the National Academy of Sciences.

[28]  R. Raines,et al.  Endowing Human Pancreatic Ribonuclease with Toxicity for Cancer Cells* , 2001, The Journal of Biological Chemistry.

[29]  M. Seno,et al.  Anti-angiogenic effect of an insertional fusion protein of human basic fibroblast growth factor and ribonuclease-1. , 2005, Protein engineering, design & selection : PEDS.

[30]  K. Michals‐Matalon,et al.  Biochemistry and Molecular Biology of Canavan Disease , 1999, Neurochemical Research.

[31]  L. Ewetz,et al.  THE ENZYMATIC OXIDATION OF CYSTEINE TO CYSTEINESULFINATE IN RAT LIVER. , 1965, Biochemical and biophysical research communications.

[32]  M. Seno,et al.  Human pancreatic RNase1-human epidermal growth factor fusion: an entirely human 'immunotoxin analog' with cytotoxic properties against squamous cell carcinomas. , 1998, Protein engineering.

[33]  J. Markley,et al.  Wheat germ cell‐free platform for eukaryotic protein production , 2006, The FEBS journal.

[34]  U. Wahn,et al.  Association and linkage of atopic dermatitis with chromosome 13q12-14 and 5q31-33 markers. , 2000, The Journal of investigative dermatology.

[35]  L. Ledoux.  Action of Ribonuclease on Certain Ascites Tumours , 1955, Nature.

[36]  J Deisenhofer,et al.  Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A. , 1996, Journal of molecular biology.

[37]  J. W. Whittaker,et al.  A tyrosine-derived free radical in apogalactose oxidase. , 1990, The Journal of biological chemistry.

[38]  G J Williams,et al.  The Protein Data Bank: a computer-based archival file for macromolecular structures. , 1978, Archives of biochemistry and biophysics.

[39]  John B. Anderson,et al.  CDD: a Conserved Domain Database for protein classification , 2004, Nucleic Acids Res..

[40]  Sam-Yong Park,et al.  Molecular Basis for the Local Conformational Rearrangement of Human Phosphoserine Phosphatase* , 2002, The Journal of Biological Chemistry.

[41]  Brian J. Smith,et al.  Structure of Leishmania mexicana phosphomannomutase highlights similarities with human isoforms. , 2006, Journal of molecular biology.

[42]  J. Duley,et al.  Pyrimidine 5′ Nucleotidase Deficiency , 2003, British journal of haematology.

[43]  Julie C. Mitchell,et al.  Disruption of shape-complementarity markers to create cytotoxic variants of ribonuclease A. , 2005, Journal of molecular biology.

[44]  M. Seno,et al.  Insertional‐fusion of basic fibroblast growth factor endowed ribonuclease 1 with enhanced cytotoxicity by steric blockade of inhibitor interaction , 2004, FEBS letters.

[45]  P. Boyer,et al.  Cystein oxygenase. II. Studies on the mechanism of the reaction with 18oxygen. , 1969, The Journal of biological chemistry.

[46]  W. S. Adams,et al.  Hereditary hemolytic anemia with human erythrocyte pyrimidine 5'-nucleotidase deficiency. , 1974, The Journal of clinical investigation.

[47]  G. Magni,et al.  Pyrimidine nucleotidases from human erythrocyte possess phosphotransferase activities specific for pyrimidine nucleotides , 1997, FEBS letters.

[48]  Karen N. Allen,et al.  The X-ray Crystal Structures of Human α-Phosphomannomutase 1 Reveal the Structural Basis of Congenital Disorder of Glycosylation Type 1a* , 2006, Journal of Biological Chemistry.

[49]  R. Raines,et al.  Ribonuclease A variants with potent cytotoxic activity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[50]  M. Seno,et al.  Epidermal growth factor receptor-dependent cytotoxicity for human squamous carcinoma cell lines of a conjugate composed of human EGF and RNase 1. , 1996, Life sciences.

[51]  Y. Kwon,et al.  Cysteine regulates expression of cysteine dioxygenase and gamma-glutamylcysteine synthetase in cultured rat hepatocytes. , 2001, American journal of physiology. Endocrinology and metabolism.

[52]  J. Markley,et al.  Probabilistic Approach to Determining Unbiased Random-coil Carbon-13 Chemical Shift Values from the Protein Chemical Shift Database , 2006, Journal of biomolecular NMR.

[53]  T. Noda,et al.  A novel genetic system to isolate a dominant negative effector on DNA-binding activity of Oct-2. , 1997, Nucleic acids research.

[54]  G. Pazour,et al.  The LC7 light chains of Chlamydomonas flagellar dyneins interact with components required for both motor assembly and regulation. , 2004, Molecular biology of the cell.

[55]  J. Sgouros,et al.  Cloning, mapping and expression of UBL3, a novel ubiquitin-like gene. , 1999, Gene.

[56]  G. Phillips,et al.  Structure of an ETHE1-like protein from Arabidopsis thaliana. , 2006, Acta crystallographica. Section D, Biological crystallography.

[57]  W. Ardelt,et al.  Cytostatic and Cytotoxic Effects of Pannon (P‐30 Protein), A Novel Anticancer Agent , 1988, Cell and tissue kinetics.

[58]  L. Ledoux.  Action of Ribonuclease on Two Solid Tumours in vivo , 1955, Nature.

[59]  P. Karplus,et al.  Crystal Structure of Mammalian Cysteine Dioxygenase , 2006, Journal of Biological Chemistry.

[60]  E. Papaleo,et al.  ETHE1 mutations are specific to ethylmalonic encephalopathy , 2005, Journal of Medical Genetics.

[61]  T. Hope,et al.  Gene Therapy Progress and Prospects: Viral trafficking during infection , 2005, Gene Therapy.

[62]  I. Kockum,et al.  Susceptibility loci for atopic dermatitis on chromosome 21 in a Swedish population , 2006, Allergy.

[63]  R. Vierstra,et al.  MUBs, a Family of Ubiquitin-fold Proteins That Are Plasma Membrane-anchored by Prenylation* , 2006, Journal of Biological Chemistry.

[64]  A. Zanella,et al.  Hereditary pyrimidine 5′‐nucleotidase deficiency: from genetics to clinical manifestations , 2006, British journal of haematology.

[65]  A. Cooper.  Biochemistry of sulfur-containing amino acids. , 1983, Annual review of biochemistry.

[66]  W. Tanner,et al.  Protein glycosylation, conserved from yeast to man: a model organism helps elucidate congenital human diseases. , 2006, Angewandte Chemie.

[67]  Jude W. Shavlik,et al.  A probabilistic approach to protein backbone tracing in electron density maps , 2006, ISMB.

[68]  A. Gronenborn,et al.  High-resolution three-dimensional structure of a single zinc finger from a human enhancer binding protein in solution. , 1992, Biochemistry.

[69]  W. Waldhäusl,et al.  Cerebral expression and serum detectability of secretagogin, a recently cloned EF-hand Ca(2+)-binding protein. , 2001, Cerebral cortex.

[70]  S. Linse,et al.  Binding of calcium ions and SNAP-25 to the hexa EF-hand protein secretagogin. , 2007, The Biochemical journal.

[71]  E. Bertini,et al.  A new syndrome with ethylmalonic aciduria and normal fatty acid oxidation in fibroblasts. , 1994, The Journal of pediatrics.

[72]  K. Vaughan,et al.  The Roadblock Light Chain Binds a Novel Region of the Cytoplasmic Dynein Intermediate Chain* , 2002, The Journal of Biological Chemistry.

[73]  T. Ørntoft,et al.  Secretagogin is a new neuroendocrine marker in the human prostate , 2007, The Prostate.

[74]  J. Collet,et al.  A New Class of Phosphotransferases Phosphorylated on an Aspartate Residue in an Amino-terminal DXDX(T/V) Motif* , 1998, The Journal of Biological Chemistry.

[75]  C. Pennell,et al.  Cytotoxicity of human RNase-based immunotoxins requires cytosolic access and resistance to ribonuclease inhibition. , 2006, Protein engineering, design & selection : PEDS.

[76]  J. Markley,et al.  Solution structure of isoform 1 of Roadblock/LC7, a light chain in the dynein complex. , 2005, Journal of molecular biology.

[77]  R. B. Kingsley,et al.  Specificity of amino acid acylases. , 1952, The Journal of biological chemistry.

[78]  John L Markley,et al.  Cell-free protein production and labeling protocol for NMR-based structural proteomics , 2004, Nature Methods.

[79]  B. Sörbo,et al.  Characteristics of the cysteinesulfinate-forming enzyme system in rat liver. , 1966, Biochimica et biophysica acta.

[80]  A M Gronenborn,et al.  High-resolution solution structure of the double Cys2His2 zinc finger from the human enhancer binding protein MBP-1. , 1992, Biochemistry.

[81]  J. W. Whittaker,et al.  Free radical catalysis by galactose oxidase. , 2003, Chemical reviews.

[82]  R. Waring,et al.  Plasma cysteine and sulphate levels in patients with motor neurone, Parkinson's and Alzheimer's disease , 1990, Neuroscience Letters.

[83]  Andreas Busjahn,et al.  A Cholesterol-Lowering Gene Maps to Chromosome 13q , 2000 .

[84]  R. Raines,et al.  KFERQ Sequence in Ribonuclease A-mediated Cytotoxicity* , 2002, The Journal of Biological Chemistry.

[85]  B. Luisi,et al.  The virtuoso of versatility: POU proteins that flex to fit. , 2000, Journal of molecular biology.

[86]  U. Arnold,et al.  Tandemization endows bovine pancreatic ribonuclease with cytotoxic activity. , 2006, Journal of molecular biology.

[87]  R. Markin,et al.  Identification of cytidine diphosphodiesters in erythrocytes from a patient with pyrimidine nucleotidase deficiency. , 1984, Blood.

[88]  G. Phillips,et al.  Protocols for production of selenomethionine-labeled proteins in 2-L polyethylene terephthalate bottles using auto-induction medium. , 2005, Protein expression and purification.

[89]  J. Moffett,et al.  N-Acetylaspartate in the CNS: From neurodiagnostics to neurobiology , 2007, Progress in Neurobiology.

[90]  M. Stipanuk.  Sulfur amino acid metabolism: pathways for production and removal of homocysteine and cysteine. , 2004, Annual review of nutrition.

[91]  M. Stipanuk,et al.  Expression, purification, and kinetic characterization of recombinant rat cysteine dioxygenase, a non-heme metalloenzyme necessary for regulation of cellular cysteine levels. , 2006, Protein expression and purification.

[92]  Eric Steffen,et al.  High efficiency single step production of expression plasmids from cDNA clones using the Flexi Vector cloning system. , 2006, Protein expression and purification.

[93]  N. Lehnert,et al.  Non-heme iron enzymes: Contrasts to heme catalysis , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Mindy I. Davis,et al.  Geometric and electronic structure/function correlations in non-heme iron enzymes. , 2000, Chemical reviews.

[95]  L. Que,et al.  Dioxygen activation at mononuclear nonheme iron active sites: enzymes, models, and intermediates. , 2004, Chemical reviews.

[96]  W. Valentine,et al.  Lead poisoning: association with hemolytic anemia, basophilic stippling, erythrocyte pyrimidine 5'-nucleotidase deficiency, and intraerythrocytic accumulation of pyrimidines. , 1976, The Journal of clinical investigation.

[97]  C. Gordon,et al.  Abnormal sulphur oxidation in systemic lupus erythematosus , 1992, The Lancet.

[98]  R. Raines,et al.  Compensating effects on the cytotoxicity of ribonuclease A variants. , 2003, Archives of biochemistry and biophysics.

[99]  George N Phillips,et al.  SOMoRe: a multi-dimensional search and optimization approach to molecular replacement. , 2003, Acta crystallographica. Section D, Biological crystallography.

[100]  E. Pardon,et al.  Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13 in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome) , 1997, Nature Genetics.

[101]  G. Phillips,et al.  Structure and mechanism of mouse cysteine dioxygenase. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[102]  L. Goldstein,et al.  Drosophila roadblock and Chlamydomonas Lc7 , 1999, The Journal of cell biology.

[103]  Peter E Wright,et al.  Solution structure of the N-terminal zinc fingers of the Xenopus laevis double-stranded RNA-binding protein ZFa. , 2005, Journal of molecular biology.

[104]  P. Sundgren,et al.  Magnetic resonance spectroscopy. , 2005, Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society.

[105]  Z. Rao,et al.  An Insight into the Mechanism of Human Cysteine Dioxygenase , 2007, Journal of Biological Chemistry.

[106]  S. Hokari,et al.  Enhanced Activity of Pyrimidine 5′-Nucleotidase in Rat Red Blood Cells during Erythropoiesis , 1998, Biological chemistry.