Protein Dynamics in Enzymatic Catalysis

Summary

Principal Investigator: Robert Callender
Abstract: DESCRIPTION (provided by applicant): The goal of this Program Project, entitled Protein Dynamics in Enzymatic Catalysis, is to study atomic motion in enzymes. We propose to study concepts of how the dynamical nature of proteins affects enzymic function and the energy landscape of enzymes from enzyme-substrate to on-enzyme transition state transition state formation. We bring together a skilled research group of diverse backgrounds all aimed at understanding enzyme function. Importantly, we bring to bear unique, advanced, and effective experimental and theoretical approaches sensitive to the evolution of protein structure on multiple time scales, from ps to minutes. There are four projects and two cores. Project 1: 'Energy Landscapes Encoding Function in LDH Investigated Over Broad Time Scales'will (1) probe how conformational motion from picoseconds to milliseconds contributes transition state formation in lactate dehydrogenase and how motions on different timescales are related to each other and (2) probe the contribution of promoting vibrations to enzymic catalysis. Project 2: 'Dynamics and the Transition State of Purine Nucleoside Phosphorylase'studies (1) the motions leading to transition state formation in PNP and (2) the nature of the transition state in PNP by locating and characterizing dynamic promoting vibrations and by generating a vibrationally altered enzyme whose local and collective bond dynamics alter the probability of reaching the transition state. Project 3: 'Mapping the Energy Landscape of Catalysis in DHFR'aims to (1) determine the dynamics of substrate binding and Michaelis complex formation and coupled protein motions in dihydrofolate reductase;(2) determine the dynamics of proton transfer in DHFR;and (3) determine the role of promoting vibrations in the catalytic reaction of DHFR. Project 4: 'Energy Landscapes and Motional Timescales in Enzyme Catalysis'investigates dynamics in enzymes on multiple time scales and provides theoretical support to the other projects by (1) investigating how longer time conformational motion contributes to enzyme function, and in atomic detail, how motions at different timescales are related to each other;(2) determining how protein architecture results in vibrational energy "channeling" in enzymes and study how mutation effects this architecture;and (3) elucidating the concept of the tight binding of the transition state and show how, in a specific reaction, the transition state is approached and transited. The Equipment Core (Core A) supports the specialized comprehensive suite of instrumentation for the Program. The Administrative Core (Core B) administers the Program Project.
Funding Period: 2004-05-01 - 2014-04-30
more information: NIH RePORT

Top Publications

  1. pmc Energy landscape of the Michaelis complex of lactate dehydrogenase: relationship to catalytic mechanism
    Huo Lei Peng
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
    Biochemistry 53:1849-57. 2014
  2. pmc Photoinduced electron transfer in folic acid investigated by ultrafast infrared spectroscopy
    Guifeng Li
    Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA
    J Phys Chem B 116:3467-75. 2012
  3. pmc The promoting vibration in human heart lactate dehydrogenase is a preferred vibrational channel
    Ardy Davarifar
    Department of Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Phys Chem B 115:15439-44. 2011
  4. pmc Femtosecond dynamics coupled to chemical barrier crossing in a Born-Oppenheimer enzyme
    Rafael G Silva
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 108:18661-5. 2011
  5. pmc Protein dynamics and enzymatic chemical barrier passage
    Dimitri Antoniou
    Departments of Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Phys Chem B 115:15147-58. 2011
  6. pmc Uridine phosphorylase from Trypanosoma cruzi: kinetic and chemical mechanisms
    Rafael G Silva
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, United States
    Biochemistry 50:9158-66. 2011
  7. pmc A model of calcium activation of the cardiac thin filament
    Edward P Manning
    Department of Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461, United States
    Biochemistry 50:7405-13. 2011
  8. pmc Isotope-edited FTIR of alkaline phosphatase resolves paradoxical ligand binding properties and suggests a role for ground-state destabilization
    Logan D Andrews
    Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305, USA
    J Am Chem Soc 133:11621-31. 2011
  9. ncbi Enzymatic transition states, transition-state analogs, dynamics, thermodynamics, and lifetimes
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Annu Rev Biochem 80:703-32. 2011
  10. pmc Conformational heterogeneity within the Michaelis complex of lactate dehydrogenase
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Phys Chem B 115:7670-8. 2011

Detail Information

Publications60

  1. pmc Energy landscape of the Michaelis complex of lactate dehydrogenase: relationship to catalytic mechanism
    Huo Lei Peng
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
    Biochemistry 53:1849-57. 2014
    ....
  2. pmc Photoinduced electron transfer in folic acid investigated by ultrafast infrared spectroscopy
    Guifeng Li
    Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA
    J Phys Chem B 116:3467-75. 2012
    ..Thus, conformations of FA that allow ultrafast intra-ET and rapid quenching of the singlet excited state play a key role in inhibiting pathological pathways following photoexcitation of FA...
  3. pmc The promoting vibration in human heart lactate dehydrogenase is a preferred vibrational channel
    Ardy Davarifar
    Department of Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Phys Chem B 115:15439-44. 2011
    ....
  4. pmc Femtosecond dynamics coupled to chemical barrier crossing in a Born-Oppenheimer enzyme
    Rafael G Silva
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 108:18661-5. 2011
    ..This study demonstrates coupling of enzymatic bond vibrations on the femtosecond time scale to barrier crossing...
  5. pmc Protein dynamics and enzymatic chemical barrier passage
    Dimitri Antoniou
    Departments of Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Phys Chem B 115:15147-58. 2011
    ....
  6. pmc Uridine phosphorylase from Trypanosoma cruzi: kinetic and chemical mechanisms
    Rafael G Silva
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, United States
    Biochemistry 50:9158-66. 2011
    ..Kinetic analysis as a function of pH indicates one protonated group essential for catalysis and for substrate binding...
  7. pmc A model of calcium activation of the cardiac thin filament
    Edward P Manning
    Department of Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461, United States
    Biochemistry 50:7405-13. 2011
    ..This model provides a valuable tool for research into the normal physiology of cardiac myofilaments and a template for studying cardiac thin filament mutations that cause human cardiomyopathies...
  8. pmc Isotope-edited FTIR of alkaline phosphatase resolves paradoxical ligand binding properties and suggests a role for ground-state destabilization
    Logan D Andrews
    Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305, USA
    J Am Chem Soc 133:11621-31. 2011
    ..These results suggest that electrostatic repulsion between Ser102 and negatively charged phosphate ester substrates contributes to catalysis by the preferential destabilization of the reaction's E·S ground state...
  9. ncbi Enzymatic transition states, transition-state analogs, dynamics, thermodynamics, and lifetimes
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Annu Rev Biochem 80:703-32. 2011
    ..Binding isotope effects (BIEs) reveal relative reactant and transition-state analog binding distortion for comparison with actual transition states...
  10. pmc Conformational heterogeneity within the Michaelis complex of lactate dehydrogenase
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Phys Chem B 115:7670-8. 2011
    ..However, conformational heterogeneity within the Michaelis complex is found that has an impact on both catalytic efficiency and thermodynamics of the enzyme...
  11. pmc Implementation of time-resolved step-scan fourier transform infrared (FT-IR) spectroscopy using a kHz repetition rate pump laser
    Donny Magana
    Department of Chemistry, Emory University, Atlanta, Georgia 300322, USA
    Appl Spectrosc 65:535-42. 2011
    ..We conclude from these studies that a substantial increase in performance of ss-FT-IR instrumentation is achieved by coupling commercial infrared benches with kHz repetition rate lasers...
  12. pmc Toward Identification of the reaction coordinate directly from the transition state ensemble using the kernel PCA method
    Dimitri Antoniou
    Department of Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Phys Chem B 115:2465-9. 2011
    ..Schwartz, S. D. Proc. Natl. Acad. Sci. U.S.A.2007, 104, 12253] and extracted a reasonable representation for the reaction coordinate...
  13. pmc Effect of osmolytes on protein dynamics in the lactate dehydrogenase-catalyzed reaction
    Nickolay Zhadin
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
    Biochemistry 50:1582-9. 2011
    ..Qualitatively, these results can be understood as an osmolyte-induced change in the energy landscape of the protein complexes, shifting the conformational nature of functional substates within the protein ensemble...
  14. pmc Slow conformational motions that favor sub-picosecond motions important for catalysis
    J R Exequiel T Pineda
    Department of Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Phys Chem B 114:15985-90. 2010
    ..We will examine how slow conformational motions bring the system to conformations that are distinguished as catalytically competent because they favor specific fast motions...
  15. pmc Investigation of catalytic loop structure, dynamics, and function relationship of Yersinia protein tyrosine phosphatase by temperature-jump relaxation spectroscopy and X-ray structural determination
    Shan Ke
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
    J Phys Chem B 116:6166-76. 2012
    ..How these competing loop properties may affect loop dynamics and enzyme function are discussed...
  16. pmc Molecular effects of familial hypertrophic cardiomyopathy-related mutations in the TNT1 domain of cTnT
    Edward P Manning
    Department of Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA
    J Mol Biol 421:54-66. 2012
    ..Finally, we compare this pathway of mutational propagation with that of the calcium activation of the thin filament and find that they are identical but opposite in direction...
  17. pmc Anisotropic energy flow and allosteric ligand binding in albumin
    Guifeng Li
    Department of Chemistry, Emory University, 1515 Dickey Dr, Atlanta, Georgia 30322, USA
    Nat Commun 5:3100. 2014
    ..This efficient energy transport mechanism enables the allosteric propagation of binding energy through the connecting helix structures. ..
  18. pmc Submillisecond mixing in a continuous-flow, microfluidic mixer utilizing mid-infrared hyperspectral imaging detection
    Drew P Kise
    Emory University, 1515 Dickey Drive, Atlanta, GA 30322, USA
    Lab Chip 14:584-91. 2014
    ....
  19. pmc Distortional binding of transition state analogs to human purine nucleoside phosphorylase probed by magic angle spinning solid-state NMR
    Mathew J Vetticatt
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, Bronx, NY 10461
    Proc Natl Acad Sci U S A 110:15991-6. 2013
    ..We conclude that hPNP stabilizes conformations of these chemically distinct analogs having distances between the cation and leaving groups resembling those of the known transition state. ..
  20. pmc Conformational freedom in tight binding enzymatic transition-state analogues
    Matthew W Motley
    Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, United States
    J Phys Chem B 117:9591-7. 2013
    ..Transition-state analogues permitting protein motion related to formation of the transition state are better mimics of the enzymatic transition state and can bind more tightly than those immobilizing catalytic site dynamics. ..
  21. pmc A simple three-dimensional-focusing, continuous-flow mixer for the study of fast protein dynamics
    Kelly S Burke
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91106, USA
    Lab Chip 13:2912-21. 2013
    ..We observe sub-millisecond kinetics that we attribute to Michaelis complex formation and loop domain closure. These results demonstrate the utility of the three-dimensional focusing mixer for biophysical studies of protein dynamics. ..
  22. pmc Changes in protein architecture and subpicosecond protein dynamics impact the reaction catalyzed by lactate dehydrogenase
    Jean E Masterson
    Department of Chemistry and Biochemistry, University of Arizona, 1306 East University Blvd, Tucson, Arizona 85721, USA
    J Phys Chem A 117:7107-13. 2013
    ..The combined results reveal the importance of the protein architecture of LDH in enzymatic catalysis by establishing how the promoting vibration is finely tuned to facilitate chemistry. ..
  23. pmc Catalytic site conformations in human PNP by 19F-NMR and crystallography
    Javier Suarez
    Department of Biochemistry, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Chem Biol 20:212-22. 2013
    ..Specific (19)F-Trp labels and X-ray crystallography provide multidimensional characterization of conformational states for free, catalytic, and inhibited complexes of human PNP...
  24. pmc Large scale dynamics of the Michaelis complex in Bacillus stearothermophilus lactate dehydrogenase revealed by a single-tryptophan mutant study
    Beining Nie
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States
    Biochemistry 52:1886-92. 2013
    ..Rather, it involves the motion of atoms spread over the protein, even some quite distal from the active site. How these results bear on the catalytic mechanism of bsLDH is discussed...
  25. pmc Transition States, analogues, and drug development
    Vern L Schramm
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx New York 10461, United States
    ACS Chem Biol 8:71-81. 2013
    ..Analogues of the transition state can bind millions of times more tightly than substrates and show promise for drug development for several targets...
  26. pmc Direct observation and control of ultrafast photoinduced twisted intramolecular charge transfer (TICT) in triphenyl-methane dyes
    Guifeng Li
    Department of Chemistry, Emory University, Atlanta, Georgia, 30322, United States
    J Phys Chem B 116:12590-6. 2012
    ..These results for MG and its analogues provide new insight regarding the dynamics and mechanism of twisted intramolecular charge transfer (TICT) in triphenylmethane dyes...
  27. pmc Direct evidence of active-site reduction and photodriven catalysis in sensitized hydrogenase assemblies
    Brandon L Greene
    Chemistry Department, Emory University, Atlanta, Georgia 30322, USA
    J Am Chem Soc 134:11108-11. 2012
    ..The possible origins of these differences and their implications for the enzymatic mechanism are discussed...
  28. pmc Conformational dynamics in human purine nucleoside phosphorylase with reactants and transition-state analogues
    Jennifer S Hirschi
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York, United States
    J Phys Chem B 114:16263-72. 2010
    ..Tight binding of the picomolar inhibitors results from increased interactions within the active site and a reduction in the number of water molecules organized within the catalytic site relative to the substrate inosine...
  29. pmc Remote mutations and active site dynamics correlate with catalytic properties of purine nucleoside phosphorylase
    Suwipa Saen-oon
    Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biophys J 94:4078-88. 2008
    ..That motion and catalysis are enhanced by mutations remote from the catalytic site implicates dynamic coupling through the protein architecture as a component of catalysis in hPNP...
  30. pmc Effects of cell volume regulating osmolytes on glycerol 3-phosphate binding to triosephosphate isomerase
    Miriam Gulotta
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 46:10055-62. 2007
    ..Results indicate that the conformational shift hypothesis alone does not account for the effects of osmolytes on Km's...
  31. pmc Reaction coordinate of an enzymatic reaction revealed by transition path sampling
    Sara L Quaytman
    Department of Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 104:12253-8. 2007
    ..In this work, we used committor distribution analysis to show that these motions are integral components of the reaction coordinate...
  32. ncbi An amalgamation of solid phase peptide synthesis and ribosomal peptide synthesis
    Jennifer J Ottesen
    Laboratory of Synthetic Protein Chemistry, The Rockefeller University, New York, NY 10021, USA
    Biopolymers 90:406-14. 2008
    ..These examples showcase the scope of the protein ligation strategy for selective introduction of isotopic labels into proteins, and the protocols described will be of value to those interested in using EPL on other systems...
  33. ncbi New mixed quantumsemiclassical propagation method
    Dimitri Antoniou
    Department of Biophysics, Albert Einstein College of Medicine, New York 10461, USA
    J Chem Phys 126:184107. 2007
    ..The test calculations they present use low-dimensional systems, in which comparison to exact quantum dynamics is feasible...
  34. pmc Ligand binding and protein dynamics in lactate dehydrogenase
    J R Exequiel T Pineda
    Department of Biophysics, Albert Einstein College of Medicine, Bronx, NY, USA
    Biophys J 93:1474-83. 2007
    ..We speculate that such a strategy for binding may be necessary to get a ligand efficiently to a binding pocket that is located fairly deep within the protein's interior...
  35. pmc Lactate dehydrogenase undergoes a substantial structural change to bind its substrate
    Linlin Qiu
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, USA
    Biophys J 93:1677-86. 2007
    ..This would be in contrast to the putative closed structure where the binding pocket resides deep within the protein interior...
  36. pmc Neighboring group participation in the transition state of human purine nucleoside phosphorylase
    Andrew S Murkin
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 46:5038-49. 2007
    ..These surprising results establish that forces in the Michaelis complex, reported by the BIEs, can be reversed or enhanced at the transition state...
  37. ncbi Loop dynamics and ligand binding kinetics in the reaction catalyzed by the Yersinia protein tyrosine phosphatase
    Mazdak Khajehpour
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 46:4370-8. 2007
    ..The significance of these dynamic results is interpreted in terms of the catalytic cycle of the enzyme...
  38. ncbi Microfluidic flow-flash: method for investigating protein dynamics
    Michael W Toepke
    Department of Chemical and Biomolecular Engineering and Department of Biochemistry, University of Illinois at Urbana Champaign, Urbana, Illinois 61801, USA
    Anal Chem 79:122-8. 2007
    ..Here, we utilize the microfluidic flow-flash method to probe the kinetics of CO recombination or O2 binding to myoglobin after the laser-induced photolysis of CO from myoglobin by UV/visible absorbance spectral imaging...
  39. ncbi Advances in time-resolved approaches to characterize the dynamical nature of enzymatic catalysis
    Robert Callender
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Chem Rev 106:3031-42. 2006
  40. ncbi Phosphate activation in the ground state of purine nucleoside phosphorylase
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Am Chem Soc 128:7765-71. 2006
    ..The electronic structure of phosphate bound with a transition state analogue differs substantially from that in the Michaelis complexes...
  41. pmc Time-resolved vibrational spectroscopy detects protein-based intermediates in the photosynthetic oxygen-evolving cycle
    Bridgette A Barry
    School of Chemistry and Biochemistry and the Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30032, USA
    Proc Natl Acad Sci U S A 103:7288-91. 2006
    ..Our results suggest that a protein-derived conformational change or proton transfer reaction precedes Mn redox reactions during the S(2)-to-S(3) and S(3)-to-S(0) transitions...
  42. ncbi Altered thermodynamics from remote mutations altering human toward bovine purine nucleoside phosphorylase
    Mahmoud Ghanem
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 47:2559-64. 2008
    ..Luo, M., Ghanem, M., Taylor, E. A., and Schramm, V. L. (2008) Biochemistry 47, 2577-2583) report changes in transition-state structure as a consequence of mutations remote from the catalytic sites of both HsPNP and BtPNP...
  43. ncbi Remote mutations alter transition-state structure of human purine nucleoside phosphorylase
    Minkui Luo
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 47:2565-76. 2008
    ..Dynamic coupling motions from the remote mutations to the catalytic sites are proposed...
  44. pmc Pyrophosphate activation in hypoxanthine--guanine phosphoribosyltransferase with transition state analogue
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 49:2705-14. 2010
    ....
  45. pmc Approximate inclusion of quantum effects in transition path sampling
    Dimitri Antoniou
    Department of Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, New York 10461, USA
    J Chem Phys 131:224111. 2009
    ..We applied this mixed centroid/classical transition path sampling method to a model system that has nontrivial quantum behavior, and showed that it can capture the correct quantum dynamical features...
  46. pmc Ribocation transition state capture and rebound in human purine nucleoside phosphorylase
    Mahmoud Ghanem
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Chem Biol 16:971-9. 2009
    ..These results establish a ribocation lifetime too short to permit capture by water. An enlarged catalytic site permits ribocation formation with relaxed geometric constraints, permitting nucleophilic rebound and N3-inosine isomerization...
  47. pmc Enzymatic transition states and dynamic motion in barrier crossing
    Steven D Schwartz
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, USA
    Nat Chem Biol 5:551-8. 2009
    ....
  48. pmc The stochastic separatrix and the reaction coordinate for complex systems
    Dimitri Antoniou
    Department of Biophysics, Albert Einstein College of Medicine Bronx, New York 10461, USA
    J Chem Phys 130:151103. 2009
    ....
  49. pmc Extension of the tryptophan chi2,1 dihedral angle-W3 band frequency relationship to a full rotation: correlations and caveats
    Laura J Juszczak
    Chemistry Department, Brooklyn College, The City University of New York, Brooklyn, New York 11210, USA
    Biochemistry 48:2777-87. 2009
    ....
  50. pmc Loop-tryptophan human purine nucleoside phosphorylase reveals submillisecond protein dynamics
    Mahmoud Ghanem
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biochemistry 48:3658-68. 2009
    ..F159W-Leuko-PNP provides a novel protein platform to investigate the protein conformational dynamics occurring prior to transition state formation...
  51. pmc Comparison studies of the human heart and Bacillus stearothermophilus lactate dehydrogreanse by transition path sampling
    Sara L Quaytman
    Department of Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    J Phys Chem A 113:1892-7. 2009
    ..stearothermophilis LDH as compared to human heart LDH. This would indicate a more variable transition process in the Bacillus enzyme...
  52. pmc Atomic detail of chemical transformation at the transition state of an enzymatic reaction
    Suwipa Saen-oon
    Departments of Biophysics and Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Ave, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 105:16543-8. 2008
    ..Dynamic motions on the femtosecond timescale provide the simultaneous optimization of these effects and coincide with transition state formation...
  53. pmc Probing the role of dynamics in hydride transfer catalyzed by lactate dehydrogenase
    Nickolay Zhadin
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Biophys J 95:1974-84. 2008
    ..The results of this study show that this approach can be applied quite generally to enzyme systems and report on the dynamic nature of proteins over a very wide time range...
  54. pmc On the pathway of forming enzymatically productive ligand-protein complexes in lactate dehydrogenase
    Hua Deng
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York, 10461, USA
    Biophys J 95:804-13. 2008
    ....
  55. ncbi Second-sphere amino acids contribute to transition-state structure in bovine purine nucleoside phosphorylase
    Lei Li
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA
    Biochemistry 47:2577-83. 2008
    ..These residues are implicated in linking the dynamic motion of the protein to formation of the transition state...
  56. ncbi Insight into catalytically relevant correlated motions in human purine nucleoside phosphorylase
    Sara Nunez
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Phys Chem A 110:463-72. 2006
    ..However, further structural data for the hPNP mutants are needed to confirm our hypothesis...

Research Grants30

  1. CENTER FOR GASTROINTESTINAL BIOLOGY AND DISEASE
    Robert S Sandler; Fiscal Year: 2013
    ..Through all of its activities, the Center improves communication, promotes collaboration, develops careers and generally enriches the intellectual climate for digestive disease research. ..
  2. Molecular Mechanisms linking Aging, Abeta Proteotoxicity and Neurodegeneration
    Jeffery W Kelly; Fiscal Year: 2013
    ..abstract_text> ..
  3. Semi-volatile PCBs: Sources, Exposures, Toxicities
    Larry W Robertson; Fiscal Year: 2013
    ..These data and dietary studies in the last Aim will provide a scientific basis for risk assessment and advice for stakeholders with the ultimate goal to protect highly-exposed individuals and populations. ..
  4. TOXIC SUBSTANCES IN THE ENVIRONMENT
    Martyn T Smith; Fiscal Year: 2013
    ..The program will be overseen and coordinated by an Administration core (A). ..
  5. Pacific Southwest RCE for Biodefense &Emerging Infectious Diseases Research
    Alan G Barbour; Fiscal Year: 2013
    ..abstract_text> ..