Enzymatic transition states and dynamic motion in barrier crossing

Steven D. Schwartz, Vern L. Schramm

Research output: Contribution to journalArticle

166 Citations (Scopus)

Abstract

What are the atomic motions at enzymatic catalytic sites on the timescale of chemical change? Combined experimental and computational chemistry approaches take advantage of transition-state analogs to reveal dynamic motions linked to transition-state formation. QM/MM transition path sampling from reactive complexes provides both temporal and dynamic information for barrier crossing. Fast (femtosecond to picosecond) dynamic motions provide essential links to enzymatic barrier crossing by local or promoting-mode dynamic searches through bond-vibrational space. Transition-state lifetimes are within the femtosecond timescales of bond vibrations and show no manifestations of stabilized, equilibrated complexes. The slow binding and protein conformational changes (microsecond to millisecond) also required for catalysis are temporally decoupled from the fast dynamic motions forming the transition state. According to this view of enzymatic catalysis, transition states are formed by fast, coincident dynamic excursions of catalytic site elements, while the binding of transition-state analogs is the conversion of the dynamic excursions to equilibrated states.

Original languageEnglish (US)
Pages (from-to)551-558
Number of pages8
JournalNature Chemical Biology
Volume5
Issue number8
DOIs
StatePublished - Aug 2009

Fingerprint

Catalysis
Catalytic Domain
Vibration
Carrier Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Enzymatic transition states and dynamic motion in barrier crossing. / Schwartz, Steven D.; Schramm, Vern L.

In: Nature Chemical Biology, Vol. 5, No. 8, 08.2009, p. 551-558.

Research output: Contribution to journalArticle

@article{6d07af1fdc4b4c2ab896eee63c249127,
title = "Enzymatic transition states and dynamic motion in barrier crossing",
abstract = "What are the atomic motions at enzymatic catalytic sites on the timescale of chemical change? Combined experimental and computational chemistry approaches take advantage of transition-state analogs to reveal dynamic motions linked to transition-state formation. QM/MM transition path sampling from reactive complexes provides both temporal and dynamic information for barrier crossing. Fast (femtosecond to picosecond) dynamic motions provide essential links to enzymatic barrier crossing by local or promoting-mode dynamic searches through bond-vibrational space. Transition-state lifetimes are within the femtosecond timescales of bond vibrations and show no manifestations of stabilized, equilibrated complexes. The slow binding and protein conformational changes (microsecond to millisecond) also required for catalysis are temporally decoupled from the fast dynamic motions forming the transition state. According to this view of enzymatic catalysis, transition states are formed by fast, coincident dynamic excursions of catalytic site elements, while the binding of transition-state analogs is the conversion of the dynamic excursions to equilibrated states.",
author = "Schwartz, {Steven D.} and Schramm, {Vern L.}",
year = "2009",
month = "8",
doi = "10.1038/nchembio.202",
language = "English (US)",
volume = "5",
pages = "551--558",
journal = "Nature Chemical Biology",
issn = "1552-4450",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Enzymatic transition states and dynamic motion in barrier crossing

AU - Schwartz, Steven D.

AU - Schramm, Vern L.

PY - 2009/8

Y1 - 2009/8

N2 - What are the atomic motions at enzymatic catalytic sites on the timescale of chemical change? Combined experimental and computational chemistry approaches take advantage of transition-state analogs to reveal dynamic motions linked to transition-state formation. QM/MM transition path sampling from reactive complexes provides both temporal and dynamic information for barrier crossing. Fast (femtosecond to picosecond) dynamic motions provide essential links to enzymatic barrier crossing by local or promoting-mode dynamic searches through bond-vibrational space. Transition-state lifetimes are within the femtosecond timescales of bond vibrations and show no manifestations of stabilized, equilibrated complexes. The slow binding and protein conformational changes (microsecond to millisecond) also required for catalysis are temporally decoupled from the fast dynamic motions forming the transition state. According to this view of enzymatic catalysis, transition states are formed by fast, coincident dynamic excursions of catalytic site elements, while the binding of transition-state analogs is the conversion of the dynamic excursions to equilibrated states.

AB - What are the atomic motions at enzymatic catalytic sites on the timescale of chemical change? Combined experimental and computational chemistry approaches take advantage of transition-state analogs to reveal dynamic motions linked to transition-state formation. QM/MM transition path sampling from reactive complexes provides both temporal and dynamic information for barrier crossing. Fast (femtosecond to picosecond) dynamic motions provide essential links to enzymatic barrier crossing by local or promoting-mode dynamic searches through bond-vibrational space. Transition-state lifetimes are within the femtosecond timescales of bond vibrations and show no manifestations of stabilized, equilibrated complexes. The slow binding and protein conformational changes (microsecond to millisecond) also required for catalysis are temporally decoupled from the fast dynamic motions forming the transition state. According to this view of enzymatic catalysis, transition states are formed by fast, coincident dynamic excursions of catalytic site elements, while the binding of transition-state analogs is the conversion of the dynamic excursions to equilibrated states.

UR - http://www.scopus.com/inward/record.url?scp=68049093016&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=68049093016&partnerID=8YFLogxK

U2 - 10.1038/nchembio.202

DO - 10.1038/nchembio.202

M3 - Article

C2 - 19620996

AN - SCOPUS:68049093016

VL - 5

SP - 551

EP - 558

JO - Nature Chemical Biology

JF - Nature Chemical Biology

SN - 1552-4450

IS - 8

ER -