Conformational dynamics and enzyme activity.

Conformational flexibility and structural fluctuations play an important role in enzyme activity. A great variety of internal motions ranging over different time scales and of different amplitudes are involved in the catalytic cycle. These different types of motions and their functional consequences are considered in the light of experimental data and theoretical analyses. The conformational changes upon substrate binding, and particularly the hinge-bending motion which occurs in enzymes made of two domains, are analyzed from several well documented examples. The conformational events accompanying the different steps of the catalytic cycle are discussed. The last section concerns the motions involved in the allosteric transition which regulates the enzyme activity.

[1]  L. Mouawad,et al.  Diagonalization in a mixed basis: A method to compute low‐frequency normal modes for large macromolecules , 1993 .

[2]  Charis Ghélis,et al.  Protein Folding , 1982 .

[3]  R W Harrison,et al.  Variational calculation of the normal modes of a large macromolecule: methods and some initial results. , 1984, Biopolymers.

[4]  M Karplus,et al.  Interdomain motion in liver alcohol dehydrogenase. Structural and energetic analysis of the hinge bending mode. , 1979, The Journal of biological chemistry.

[5]  David Pérahia,et al.  Computation of Low-frequency Normal Modes in Macromolecules: Improvements to the Method of Diagonalization in a Mixed Basis and Application to Hemoglobin , 1995, Comput. Chem..

[6]  F. Van Vliet,et al.  The catalytic site of Escherichia coli aspartate transcarbamylase: interaction between histidine 134 and the carbonyl group of the substrate carbamyl phosphate. , 1990, Biochemistry.

[7]  F. Cohen,et al.  A "helix-scissors" mechanism for the hinge-bending conformational change in phosphoglycerate kinase. , 2009, International journal of peptide and protein research.

[8]  P. Deschavanne,et al.  Conformational adaptability of the active site of beta-galactosidase. Interaction of the enzyme with some substrate analogous effectors. , 1978, The Journal of biological chemistry.

[9]  H. Watson,et al.  NMR analysis of the interdomain region of yeast phosphoglycerate kinase. , 1988, European journal of biochemistry.

[10]  Ming‐Hong Hao,et al.  Analyzing the normal mode dynamics of macromolecules by the component synthesis method: Residue clustering and multiple‐component approach , 1992, Biopolymers.

[11]  K Harlos,et al.  Crystal structure of the binary complex of pig muscle phosphoglycerate kinase and its substrate 3‐phospho‐D‐glycerate , 1992, Proteins.

[12]  R. Huber,et al.  Crystallographic refinement and atomic models of two different forms of citrate synthase at 2.7 and 1.7 A resolution. , 1984, Journal of molecular biology.

[13]  F. Gurd,et al.  Motions in proteins. , 1979, Advances in protein chemistry.

[14]  J. Knowles,et al.  To build an enzyme.... , 1991, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[15]  Philip R. Evans,et al.  Structural basis of the allosteric behaviour of phosphofructokinase , 1990, Nature.

[16]  G. Reeke,et al.  The structure of carboxypeptidase a, vi. Some results at 2.0-a resolution, and the complex with glycyl-tyrosine at 2.8-a resolution. , 1967, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Daniel E. Koshland,et al.  Competitive Inhibition by Substrate during Enzyme Action. Evidence for the Induced-fit Theory1,2 , 1960 .

[18]  O. Ptitsyn,et al.  Correlation between enzyme activity and hinge-bending domain displacement in 3-phosphoglycerate kinase. , 1989, European journal of biochemistry.

[19]  G Careri,et al.  Enzyme dynamics: the statistical physics approach. , 1979, Annual review of biophysics and bioengineering.

[20]  J. Changeux,et al.  ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL. , 1965, Journal of molecular biology.

[21]  J. D. Gregory,et al.  Arrangement of substrates at the active site of yeast phosphoglycerate kinase. Effect of sulfate ion. , 1993, The Journal of biological chemistry.

[22]  A. Lesk,et al.  Structural mechanisms for domain movements in proteins. , 1994, Biochemistry.

[23]  Robert Huber,et al.  Conformational flexibility and its functional significance in some protein molecules , 1979 .

[24]  P. Evans,et al.  Sequence, structure and activity of phosphoglycerate kinase: a possible hinge-bending enzyme , 1979, Nature.

[25]  M. Karplus,et al.  Multiple conformational states of proteins: a molecular dynamics analysis of myoglobin. , 1987, Science.

[26]  J. Yon.  Spécificité dynamique en biologie , 1976 .

[27]  Jürgen Schlitter,et al.  Targeted Molecular Dynamics Simulation of Conformational Change-Application to the T ↔ R Transition in Insulin , 1993 .

[28]  M. Karplus,et al.  The hinge-bending mode in lysozyme , 1976, Nature.

[29]  G Careri,et al.  Statistical time events in enzymes: a physical assessment. , 1975, CRC critical reviews in biochemistry.

[30]  G. Weber.  Ligand binding and internal equilibria in proteins. , 1972, Biochemistry.

[31]  C. Dobson,et al.  Conformational mobility within the structure of muscular parvalbumins. An NMR study of the aromatic resonances of phenylalanine residues , 1976, FEBS letters.

[32]  A. R. Tammar,et al.  Protein Structure and Enzyme Activity , 1985 .

[33]  S J Remington,et al.  Citrate synthase: structure, control, and mechanism. , 1986, Annual review of biophysics and biophysical chemistry.

[34]  Y. Sanejouand,et al.  Hinge‐bending motion in citrate synthase arising from normal mode calculations , 1995, Proteins.

[35]  T. McPhillips,et al.  Structure of the R65Q mutant of yeast 3-phosphoglycerate kinase complexed with Mg-AMP-PNP and 3-phospho-D-glycerate. , 1996, Biochemistry.

[36]  D Perahia,et al.  Motions in hemoglobin studied by normal mode analysis and energy minimization: evidence for the existence of tertiary T-like, quaternary R-like intermediate structures. , 1996, Journal of molecular biology.

[37]  L. Young,et al.  Catalysis by entropic guidance from enzymes. , 1996, Biochemistry.

[38]  M. Karplus,et al.  Proteins: A Theoretical Perspective of Dynamics, Structure, and Thermodynamics , 1988 .

[39]  David Perahia,et al.  A method to explore transition paths in macromolecules. Applications to hemoglobin and phosphoglycerate kinase , 1995 .

[40]  M. Desmadril,et al.  Conformational changes in yeast phosphoglycerate kinase upon ligand binding: Fluorescence of a linked probe and chemical reactivity of genetically introduced cysteinyl residues , 1991, Proteins: Structure, Function, and Bioinformatics.

[41]  A. Pardee,et al.  [124b] Aspartate transcarbamylase from Escherichia coli: Aspartate + carbamyl phosphate → Carbamyl aspartate + Pi + H+ , 1962 .

[42]  Y. Sanejouand,et al.  A new approach for determining low‐frequency normal modes in macromolecules , 1994 .

[43]  J. Lakowicz,et al.  Quenching of protein fluorescence by oxygen. Detection of structural fluctuations in proteins on the nanosecond time scale. , 1973, Biochemistry.

[44]  H. Watson,et al.  The structure of a thermally stable 3‐phosphoglycerate kinase and a comparison with its mesophilic equivalent , 1993, Proteins.

[45]  J. Durup,et al.  Theoretical determination of conformational paths in citrate synthase , 1992, Biopolymers.

[46]  J. Feeney,et al.  1H nuclear magnetic resonance studies of the tyrosine residues of selectively deuterated Lactobacillus casei dihydrofolate reductase , 1977, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[47]  J. Ricard,et al.  Regulatory Behavior of Monomeric Enzymes , 1974 .

[48]  J. Yon,et al.  Nucleophilic competition in some -galactosidase-catalyzed reactions. , 1973, European journal of biochemistry.

[49]  H. Watson,et al.  NMR analysis of site-specific mutants of yeast phosphoglycerate kinase. An investigation of the triose-binding site. , 1989, European journal of biochemistry.

[50]  R. Scopes.  The Steady‐State Kinetics of Yeast Phosphoglycerate Kinase , 1978 .

[51]  B. Sykes,et al.  Fluorotyrosine alkaline phosphatase: internal mobility of individual tyrosines and the role of chemical shift anisotropy as a 19F nuclear spin relaxation mechanism in proteins. , 1975, Journal of molecular biology.

[52]  K. Wüthrich,et al.  Dynamic model of globular protein conformations based on NMR studies in solution , 1978, Nature.

[53]  Frederic M. Richards,et al.  Packing of α-helices: Geometrical constraints and contact areas☆ , 1978 .

[54]  D. Koshland,et al.  The catalytic and regulatory properties of enzymes. , 1968, Annual review of biochemistry.

[55]  R. Huber,et al.  Functional significance of flexibility in proteins , 1982, Biopolymers.

[56]  Bradley E. Bernstein,et al.  Synergistic effects of substrate-induced conformational changes in phosphoglycerate kinase activation , 1997, Nature.

[57]  P. Wolynes,et al.  The energy landscapes and motions of proteins. , 1991, Science.

[58]  D. Koshland,et al.  Comparison of experimental binding data and theoretical models in proteins containing subunits. , 1966, Biochemistry.

[59]  J M Yon,et al.  The effects of ligands on the conformation of phosphoglycerate kinase: Fluorescence anisotropy decay and theoretical interpretation , 1990, Biopolymers.

[60]  A. Thomas,et al.  Analysis of the low-frequency normal modes of the R state of aspartate transcarbamylase and a comparison with the T state modes. , 1996, Journal of molecular biology.

[61]  M. Karplus,et al.  The hinge‐bending mode of a lysozyme–inhibitor complex , 1986, Biopolymers.

[62]  H. Watson,et al.  Site‐directed mutagenesis of histidine 62 in the ‘basic patch’ region of yeast phosphoglycerate kinase , 1989, FEBS letters.

[63]  R. J. Williams,et al.  Nuclear-magnetic-resonance study of the active-site structure of yeast phosphoglycerate kinase. , 1976, European journal of biochemistry.

[64]  R. Jaenicke,et al.  Enzymes under extremes of physical conditions. , 1981, Annual review of biophysics and bioengineering.

[65]  K. Wüthrich,et al.  1H NMR studies at 360 MHz of the aromatic amino acid residues in ferrocytochrome c-552 from Euglena gracilis. , 1977, Biochimica et Biophysica Acta.

[66]  C. Dobson,et al.  The study of conformational states of proteins by nuclear magnetic resonance. , 1985, The Biochemical journal.

[67]  K. Harlos,et al.  2.0 Å resolution structure of a ternary complex of pig muscle phosphoglycerate kinase containing 3‐phospho‐D‐glycerate and the nucleotide Mn adenylylimidodiphosphate , 1996, Proteins.

[68]  Robert J.P. Williams.  The functions of structure and dynamics in proteins, peptides and metal ion complexes and their relationships to biological recognition and the handling of information , 1987 .

[69]  S. Bernhard,et al.  On the relationship between the conformation and the catalyzed reactivity of acyl-chymotrypsin. , 1971, Journal of molecular biology.

[70]  C. Dobson,et al.  Proton magnetic resonance studies of the tyrosine residues of hen lysozyme-assignment and detection of conformational mobility , 1975, Proceedings of the Royal Society of London. Series B. Biological Sciences.

[71]  M Karplus,et al.  The internal dynamics of globular proteins. , 1981, CRC critical reviews in biochemistry.

[72]  E. Kantrowitz,et al.  A possible model for the concerted allosteric transition in Escherichia coli aspartate transcarbamylase as deduced from site-directed mutagenesis studies. , 1988, Biochemistry.

[73]  D. Phillips,et al.  Crystallographic studies of the dynamic properties of lysozyme , 1979, Nature.

[74]  A. Thomas,et al.  Analysis of the low frequency normal modes of the T-state of aspartate transcarbamylase. , 1996, Journal of molecular biology.

[75]  O. Jardetzky,et al.  Carbon-13 nuclear magnetic resonance study of molecular motions and conformational transitions in muscle calcium binding parvalbumins , 1976 .

[76]  S. Benkovic,et al.  A perspective on biological catalysis , 1996, Nature Structural Biology.

[77]  M. Karplus,et al.  Conjugate peak refinement: an algorithm for finding reaction paths and accurate transition states in systems with many degrees of freedom , 1992 .

[78]  D. Agard,et al.  Conformational substates in enzyme mechanism: The 120 K structure of α‐lytic protease at 1.5 Å resolution , 1997, Protein science : a publication of the Protein Society.

[79]  M. Sternberg,et al.  Dynamic information from protein crystallography. An analysis of temperature factors from refinement of the hen egg-white lysozyme structure. , 1979, Journal of molecular biology.

[80]  M. Karplus,et al.  Normal modes for specific motions of macromolecules: application to the hinge-bending mode of lysozyme. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[81]  T. Steitz,et al.  Substrate binding closes the cleft between the domains of yeast phosphoglycerate kinase. , 1979, The Journal of biological chemistry.

[82]  C. Woodward,et al.  Hydrogen exchange kinetics and internal motions in proteins and nucleic acids. , 1979, Annual review of biophysics and bioengineering.

[83]  M. Karplus,et al.  Dynamics of folded proteins , 1977, Nature.

[84]  Ron Elber,et al.  A method for determining reaction paths in large molecules: application to myoglobin , 1987 .

[85]  H. Watson,et al.  Sequence and structure of yeast phosphoglycerate kinase. , 1982, The EMBO journal.

[86]  R. Lavery,et al.  An analysis of the conformational paths of citrate synthase , 1993, Proteins: Structure, Function, and Bioinformatics.

[87]  W. Lipscomb,et al.  Complex of N-phosphonacetyl-L-aspartate with aspartate carbamoyltransferase. X-ray refinement, analysis of conformational changes and catalytic and allosteric mechanisms. , 1988, Journal of molecular biology.