Flexibility, diversity, and cooperativity: Pillars of enzyme catalysis

Gordon G. Hammes, Stephen J. Benkovic, Sharon Hammes-Schiffer

Research output: Contribution to journalArticle

145 Citations (Scopus)

Abstract

This brief review discusses our current understanding of the molecular basis of enzyme catalysis. A historical development is presented, beginning with steady state kinetics and progressing through modern fast reaction methods, nuclear magnetic resonance, and single-molecule fluorescence techniques. Experimental results are summarized for ribonuclease, aspartate aminotransferase, and especially dihydrofolate reductase (DHFR). Multiple intermediates, multiple conformations, and cooperative conformational changes are shown to be an essential part of virtually all enzyme mechanisms. In the case of DHFR, theoretical investigations have provided detailed information about the movement of atoms within the enzyme-substrate complex as the reaction proceeds along the collective reaction coordinate for hydride transfer. A general mechanism is presented for enzyme catalysis that includes multiple intermediates and a complex, multidimensional standard free energy surface. Protein flexibility, diverse protein conformations, and cooperative conformational changes are important features of this model.

Original languageEnglish (US)
Pages (from-to)10422-10430
Number of pages9
JournalBiochemistry
Volume50
Issue number48
DOIs
StatePublished - Dec 6 2011

Fingerprint

Catalysis
Tetrahydrofolate Dehydrogenase
Enzymes
Conformations
Protein Conformation
Ribonucleases
Aspartate Aminotransferases
Hydrides
Free energy
Proteins
Magnetic Resonance Spectroscopy
Fluorescence
Nuclear magnetic resonance
Atoms
Molecules
Kinetics
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry

Cite this

Hammes, G. G., Benkovic, S. J., & Hammes-Schiffer, S. (2011). Flexibility, diversity, and cooperativity: Pillars of enzyme catalysis. Biochemistry, 50(48), 10422-10430. https://doi.org/10.1021/bi201486f
Hammes, Gordon G. ; Benkovic, Stephen J. ; Hammes-Schiffer, Sharon. / Flexibility, diversity, and cooperativity : Pillars of enzyme catalysis. In: Biochemistry. 2011 ; Vol. 50, No. 48. pp. 10422-10430.
@article{557f82dbfdd346c7a6a1dcbf00159a8f,
title = "Flexibility, diversity, and cooperativity: Pillars of enzyme catalysis",
abstract = "This brief review discusses our current understanding of the molecular basis of enzyme catalysis. A historical development is presented, beginning with steady state kinetics and progressing through modern fast reaction methods, nuclear magnetic resonance, and single-molecule fluorescence techniques. Experimental results are summarized for ribonuclease, aspartate aminotransferase, and especially dihydrofolate reductase (DHFR). Multiple intermediates, multiple conformations, and cooperative conformational changes are shown to be an essential part of virtually all enzyme mechanisms. In the case of DHFR, theoretical investigations have provided detailed information about the movement of atoms within the enzyme-substrate complex as the reaction proceeds along the collective reaction coordinate for hydride transfer. A general mechanism is presented for enzyme catalysis that includes multiple intermediates and a complex, multidimensional standard free energy surface. Protein flexibility, diverse protein conformations, and cooperative conformational changes are important features of this model.",
author = "Hammes, {Gordon G.} and Benkovic, {Stephen J.} and Sharon Hammes-Schiffer",
year = "2011",
month = "12",
day = "6",
doi = "10.1021/bi201486f",
language = "English (US)",
volume = "50",
pages = "10422--10430",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "48",

}

Hammes, GG, Benkovic, SJ & Hammes-Schiffer, S 2011, 'Flexibility, diversity, and cooperativity: Pillars of enzyme catalysis', Biochemistry, vol. 50, no. 48, pp. 10422-10430. https://doi.org/10.1021/bi201486f

Flexibility, diversity, and cooperativity : Pillars of enzyme catalysis. / Hammes, Gordon G.; Benkovic, Stephen J.; Hammes-Schiffer, Sharon.

In: Biochemistry, Vol. 50, No. 48, 06.12.2011, p. 10422-10430.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Flexibility, diversity, and cooperativity

T2 - Pillars of enzyme catalysis

AU - Hammes, Gordon G.

AU - Benkovic, Stephen J.

AU - Hammes-Schiffer, Sharon

PY - 2011/12/6

Y1 - 2011/12/6

N2 - This brief review discusses our current understanding of the molecular basis of enzyme catalysis. A historical development is presented, beginning with steady state kinetics and progressing through modern fast reaction methods, nuclear magnetic resonance, and single-molecule fluorescence techniques. Experimental results are summarized for ribonuclease, aspartate aminotransferase, and especially dihydrofolate reductase (DHFR). Multiple intermediates, multiple conformations, and cooperative conformational changes are shown to be an essential part of virtually all enzyme mechanisms. In the case of DHFR, theoretical investigations have provided detailed information about the movement of atoms within the enzyme-substrate complex as the reaction proceeds along the collective reaction coordinate for hydride transfer. A general mechanism is presented for enzyme catalysis that includes multiple intermediates and a complex, multidimensional standard free energy surface. Protein flexibility, diverse protein conformations, and cooperative conformational changes are important features of this model.

AB - This brief review discusses our current understanding of the molecular basis of enzyme catalysis. A historical development is presented, beginning with steady state kinetics and progressing through modern fast reaction methods, nuclear magnetic resonance, and single-molecule fluorescence techniques. Experimental results are summarized for ribonuclease, aspartate aminotransferase, and especially dihydrofolate reductase (DHFR). Multiple intermediates, multiple conformations, and cooperative conformational changes are shown to be an essential part of virtually all enzyme mechanisms. In the case of DHFR, theoretical investigations have provided detailed information about the movement of atoms within the enzyme-substrate complex as the reaction proceeds along the collective reaction coordinate for hydride transfer. A general mechanism is presented for enzyme catalysis that includes multiple intermediates and a complex, multidimensional standard free energy surface. Protein flexibility, diverse protein conformations, and cooperative conformational changes are important features of this model.

UR - http://www.scopus.com/inward/record.url?scp=82455219011&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=82455219011&partnerID=8YFLogxK

U2 - 10.1021/bi201486f

DO - 10.1021/bi201486f

M3 - Article

C2 - 22029278

AN - SCOPUS:82455219011

VL - 50

SP - 10422

EP - 10430

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 48

ER -

Hammes GG, Benkovic SJ, Hammes-Schiffer S. Flexibility, diversity, and cooperativity: Pillars of enzyme catalysis. Biochemistry. 2011 Dec 6;50(48):10422-10430. https://doi.org/10.1021/bi201486f