Network of coupled promoting motions in enzyme catalysis

Pratul K. Agarwal, Salomon R. Billeter, P. T.Ravi Rajagopalan, Stephen J. Benkovic, Sharon Hammes-Schiffer

Research output: Contribution to journalArticle

369 Citations (Scopus)

Abstract

A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified and characterized. The present identification is based on genomic analysis for sequence conservation, kinetic measurements of multiple mutations, and mixed quantum/classical molecular dynamics simulations of hydride transfer. The motions in this network span time scales of femtoseconds to milliseconds and are found on the exterior of the enzyme as well as in the active site. This type of network has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site.

Original languageEnglish (US)
Pages (from-to)2794-2799
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number5
DOIs
StatePublished - Mar 5 2002

Fingerprint

Catalysis
Catalytic Domain
Protein Engineering
Tetrahydrofolate Dehydrogenase
Enzymes
Molecular Dynamics Simulation
Sequence Analysis
Mutation
Pharmaceutical Preparations
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Agarwal, P. K., Billeter, S. R., Rajagopalan, P. T. R., Benkovic, S. J., & Hammes-Schiffer, S. (2002). Network of coupled promoting motions in enzyme catalysis. Proceedings of the National Academy of Sciences of the United States of America, 99(5), 2794-2799. https://doi.org/10.1073/pnas.052005999
Agarwal, Pratul K. ; Billeter, Salomon R. ; Rajagopalan, P. T.Ravi ; Benkovic, Stephen J. ; Hammes-Schiffer, Sharon. / Network of coupled promoting motions in enzyme catalysis. In: Proceedings of the National Academy of Sciences of the United States of America. 2002 ; Vol. 99, No. 5. pp. 2794-2799.
@article{8d19aeb835574eb9af7f4a0c71b40890,
title = "Network of coupled promoting motions in enzyme catalysis",
abstract = "A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified and characterized. The present identification is based on genomic analysis for sequence conservation, kinetic measurements of multiple mutations, and mixed quantum/classical molecular dynamics simulations of hydride transfer. The motions in this network span time scales of femtoseconds to milliseconds and are found on the exterior of the enzyme as well as in the active site. This type of network has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site.",
author = "Agarwal, {Pratul K.} and Billeter, {Salomon R.} and Rajagopalan, {P. T.Ravi} and Benkovic, {Stephen J.} and Sharon Hammes-Schiffer",
year = "2002",
month = "3",
day = "5",
doi = "10.1073/pnas.052005999",
language = "English (US)",
volume = "99",
pages = "2794--2799",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "5",

}

Agarwal, PK, Billeter, SR, Rajagopalan, PTR, Benkovic, SJ & Hammes-Schiffer, S 2002, 'Network of coupled promoting motions in enzyme catalysis', Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 5, pp. 2794-2799. https://doi.org/10.1073/pnas.052005999

Network of coupled promoting motions in enzyme catalysis. / Agarwal, Pratul K.; Billeter, Salomon R.; Rajagopalan, P. T.Ravi; Benkovic, Stephen J.; Hammes-Schiffer, Sharon.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 99, No. 5, 05.03.2002, p. 2794-2799.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Network of coupled promoting motions in enzyme catalysis

AU - Agarwal, Pratul K.

AU - Billeter, Salomon R.

AU - Rajagopalan, P. T.Ravi

AU - Benkovic, Stephen J.

AU - Hammes-Schiffer, Sharon

PY - 2002/3/5

Y1 - 2002/3/5

N2 - A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified and characterized. The present identification is based on genomic analysis for sequence conservation, kinetic measurements of multiple mutations, and mixed quantum/classical molecular dynamics simulations of hydride transfer. The motions in this network span time scales of femtoseconds to milliseconds and are found on the exterior of the enzyme as well as in the active site. This type of network has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site.

AB - A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified and characterized. The present identification is based on genomic analysis for sequence conservation, kinetic measurements of multiple mutations, and mixed quantum/classical molecular dynamics simulations of hydride transfer. The motions in this network span time scales of femtoseconds to milliseconds and are found on the exterior of the enzyme as well as in the active site. This type of network has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site.

UR - http://www.scopus.com/inward/record.url?scp=0037022683&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037022683&partnerID=8YFLogxK

U2 - 10.1073/pnas.052005999

DO - 10.1073/pnas.052005999

M3 - Article

C2 - 11867722

AN - SCOPUS:0037022683

VL - 99

SP - 2794

EP - 2799

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 5

ER -