On the origin of the chemical barrier and tunneling in enzymes

Sara Quaytman MacHleder, J. R Exequiel T Pineda, Steven D Schwartz

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

This paper presents both a review of some recent results from our group and experimental groups, and some new theoretical results all of which are helping to form a more physically rigorous picture of the process of enzymatic catalysis. A common classical picture of enzymatic catalysis is the transition state tight binding model. Schwartz and Schramm (Nat. Chem. Biol. 2009, 5, 551-558.) have recently argued from both theoretical and experimental results that this picture is incorrect.We now investigate what the nature of barriers might be in enzymatic reactions, and what this viewpoint might imply for tunneling in a hydrogen transfer enzyme. For lactate dehydrogenase we conclude that the enzymes role in catalysis is at least partially to hunt through configuration space for those configurations that minimize chemical free energy barriers. Those configurations do not seem to be stable basins on the free energy surface, and in fact the overall free energy barrier to reaction may well largely be due to this stochastic hunt - both probabilistically and energetically. We suggest further computations to test this hypothesis.

Original languageEnglish (US)
Pages (from-to)690-695
Number of pages6
JournalJournal of Physical Organic Chemistry
Volume23
Issue number7
DOIs
StatePublished - Jul 2010
Externally publishedYes

Fingerprint

Catalysis
Free energy
catalysis
enzymes
Energy barriers
free energy
Enzymes
configurations
lactates
dehydrogenases
L-Lactate Dehydrogenase
Hydrogen
hydrogen

Keywords

  • Conformational fluctuation
  • Free energy barrier
  • Potential energy
  • Promoting vibration

ASJC Scopus subject areas

  • Organic Chemistry
  • Physical and Theoretical Chemistry

Cite this

On the origin of the chemical barrier and tunneling in enzymes. / MacHleder, Sara Quaytman; Pineda, J. R Exequiel T; Schwartz, Steven D.

In: Journal of Physical Organic Chemistry, Vol. 23, No. 7, 07.2010, p. 690-695.

Research output: Contribution to journalArticle

MacHleder, Sara Quaytman ; Pineda, J. R Exequiel T ; Schwartz, Steven D. / On the origin of the chemical barrier and tunneling in enzymes. In: Journal of Physical Organic Chemistry. 2010 ; Vol. 23, No. 7. pp. 690-695.
@article{04078bc7b2414d93b9d9220429b4e8f4,
title = "On the origin of the chemical barrier and tunneling in enzymes",
abstract = "This paper presents both a review of some recent results from our group and experimental groups, and some new theoretical results all of which are helping to form a more physically rigorous picture of the process of enzymatic catalysis. A common classical picture of enzymatic catalysis is the transition state tight binding model. Schwartz and Schramm (Nat. Chem. Biol. 2009, 5, 551-558.) have recently argued from both theoretical and experimental results that this picture is incorrect.We now investigate what the nature of barriers might be in enzymatic reactions, and what this viewpoint might imply for tunneling in a hydrogen transfer enzyme. For lactate dehydrogenase we conclude that the enzymes role in catalysis is at least partially to hunt through configuration space for those configurations that minimize chemical free energy barriers. Those configurations do not seem to be stable basins on the free energy surface, and in fact the overall free energy barrier to reaction may well largely be due to this stochastic hunt - both probabilistically and energetically. We suggest further computations to test this hypothesis.",
keywords = "Conformational fluctuation, Free energy barrier, Potential energy, Promoting vibration",
author = "MacHleder, {Sara Quaytman} and Pineda, {J. R Exequiel T} and Schwartz, {Steven D}",
year = "2010",
month = "7",
doi = "10.1002/poc.1688",
language = "English (US)",
volume = "23",
pages = "690--695",
journal = "Journal of Physical Organic Chemistry",
issn = "0894-3230",
publisher = "John Wiley and Sons Ltd",
number = "7",

}

TY - JOUR

T1 - On the origin of the chemical barrier and tunneling in enzymes

AU - MacHleder, Sara Quaytman

AU - Pineda, J. R Exequiel T

AU - Schwartz, Steven D

PY - 2010/7

Y1 - 2010/7

N2 - This paper presents both a review of some recent results from our group and experimental groups, and some new theoretical results all of which are helping to form a more physically rigorous picture of the process of enzymatic catalysis. A common classical picture of enzymatic catalysis is the transition state tight binding model. Schwartz and Schramm (Nat. Chem. Biol. 2009, 5, 551-558.) have recently argued from both theoretical and experimental results that this picture is incorrect.We now investigate what the nature of barriers might be in enzymatic reactions, and what this viewpoint might imply for tunneling in a hydrogen transfer enzyme. For lactate dehydrogenase we conclude that the enzymes role in catalysis is at least partially to hunt through configuration space for those configurations that minimize chemical free energy barriers. Those configurations do not seem to be stable basins on the free energy surface, and in fact the overall free energy barrier to reaction may well largely be due to this stochastic hunt - both probabilistically and energetically. We suggest further computations to test this hypothesis.

AB - This paper presents both a review of some recent results from our group and experimental groups, and some new theoretical results all of which are helping to form a more physically rigorous picture of the process of enzymatic catalysis. A common classical picture of enzymatic catalysis is the transition state tight binding model. Schwartz and Schramm (Nat. Chem. Biol. 2009, 5, 551-558.) have recently argued from both theoretical and experimental results that this picture is incorrect.We now investigate what the nature of barriers might be in enzymatic reactions, and what this viewpoint might imply for tunneling in a hydrogen transfer enzyme. For lactate dehydrogenase we conclude that the enzymes role in catalysis is at least partially to hunt through configuration space for those configurations that minimize chemical free energy barriers. Those configurations do not seem to be stable basins on the free energy surface, and in fact the overall free energy barrier to reaction may well largely be due to this stochastic hunt - both probabilistically and energetically. We suggest further computations to test this hypothesis.

KW - Conformational fluctuation

KW - Free energy barrier

KW - Potential energy

KW - Promoting vibration

UR - http://www.scopus.com/inward/record.url?scp=77955165752&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955165752&partnerID=8YFLogxK

U2 - 10.1002/poc.1688

DO - 10.1002/poc.1688

M3 - Article

AN - SCOPUS:77955165752

VL - 23

SP - 690

EP - 695

JO - Journal of Physical Organic Chemistry

JF - Journal of Physical Organic Chemistry

SN - 0894-3230

IS - 7

ER -