Understanding the enzymatic activity of 4-oxalocrotonate tautomerase and its mutant analogues: a computational study

Tell Tuttle, Ehud Keinan, Walter Thiel

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The effect of replacing arginine residues (Arg) with citrulline residues (Cit) in the binding site of 4-oxalocrotonate tautomerase (4-OT) was investigated with force field molecular dynamics and hybrid quantum mechanics/molecular mechanics studies. It is found that the Arg61Cit mutation has only minor effects on the kcat and KM values determined experimentally because of the flexibility of this residue. The decrease in kcat and increase in KM for the Arg11Cit and Arg39Cit mutations are due to the disruption of the binding site, which arises from repulsive interactions with neighboring residues. The results of this investigation shed new light on the effects of mutations in the binding site of 4-OT and consequently on how the enzyme binds the active substrate.

LanguageEnglish
Pages19685-19695
Number of pages11
JournalJournal of Physical Chemistry B
Volume110
Issue number39
Early online date13 Sep 2006
DOIs
Publication statusPublished - 5 Oct 2006

Fingerprint

Binding sites
mutations
Binding Sites
analogs
Citrulline
Arginine
Molecular mechanics
Quantum theory
Molecular dynamics
Enzymes
field theory (physics)
enzymes
quantum mechanics
flexibility
Substrates
molecular dynamics
4-oxalocrotonate tautomerase
interactions

Keywords

  • force field molecular dynamics
  • binding
  • mutations
  • enzymes

Cite this

@article{b6613e63d3324a07b9322e767fa2b51c,
title = "Understanding the enzymatic activity of 4-oxalocrotonate tautomerase and its mutant analogues: a computational study",
abstract = "The effect of replacing arginine residues (Arg) with citrulline residues (Cit) in the binding site of 4-oxalocrotonate tautomerase (4-OT) was investigated with force field molecular dynamics and hybrid quantum mechanics/molecular mechanics studies. It is found that the Arg61Cit mutation has only minor effects on the kcat and KM values determined experimentally because of the flexibility of this residue. The decrease in kcat and increase in KM for the Arg11Cit and Arg39Cit mutations are due to the disruption of the binding site, which arises from repulsive interactions with neighboring residues. The results of this investigation shed new light on the effects of mutations in the binding site of 4-OT and consequently on how the enzyme binds the active substrate.",
keywords = "force field molecular dynamics, binding, mutations, enzymes",
author = "Tell Tuttle and Ehud Keinan and Walter Thiel",
year = "2006",
month = "10",
day = "5",
doi = "10.1021/jp0634858",
language = "English",
volume = "110",
pages = "19685--19695",
journal = "Journal of Physical Chemistry B",
issn = "1520-6106",
publisher = "American Chemical Society",
number = "39",

}

Understanding the enzymatic activity of 4-oxalocrotonate tautomerase and its mutant analogues : a computational study. / Tuttle, Tell; Keinan, Ehud; Thiel, Walter.

In: Journal of Physical Chemistry B , Vol. 110, No. 39, 05.10.2006, p. 19685-19695.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Understanding the enzymatic activity of 4-oxalocrotonate tautomerase and its mutant analogues

T2 - Journal of Physical Chemistry B

AU - Tuttle, Tell

AU - Keinan, Ehud

AU - Thiel, Walter

PY - 2006/10/5

Y1 - 2006/10/5

N2 - The effect of replacing arginine residues (Arg) with citrulline residues (Cit) in the binding site of 4-oxalocrotonate tautomerase (4-OT) was investigated with force field molecular dynamics and hybrid quantum mechanics/molecular mechanics studies. It is found that the Arg61Cit mutation has only minor effects on the kcat and KM values determined experimentally because of the flexibility of this residue. The decrease in kcat and increase in KM for the Arg11Cit and Arg39Cit mutations are due to the disruption of the binding site, which arises from repulsive interactions with neighboring residues. The results of this investigation shed new light on the effects of mutations in the binding site of 4-OT and consequently on how the enzyme binds the active substrate.

AB - The effect of replacing arginine residues (Arg) with citrulline residues (Cit) in the binding site of 4-oxalocrotonate tautomerase (4-OT) was investigated with force field molecular dynamics and hybrid quantum mechanics/molecular mechanics studies. It is found that the Arg61Cit mutation has only minor effects on the kcat and KM values determined experimentally because of the flexibility of this residue. The decrease in kcat and increase in KM for the Arg11Cit and Arg39Cit mutations are due to the disruption of the binding site, which arises from repulsive interactions with neighboring residues. The results of this investigation shed new light on the effects of mutations in the binding site of 4-OT and consequently on how the enzyme binds the active substrate.

KW - force field molecular dynamics

KW - binding

KW - mutations

KW - enzymes

UR - http://www.scopus.com/inward/record.url?scp=33750371435&partnerID=8YFLogxK

UR - https://pubs.acs.org/journal/jpcbfk

U2 - 10.1021/jp0634858

DO - 10.1021/jp0634858

M3 - Article

VL - 110

SP - 19685

EP - 19695

JO - Journal of Physical Chemistry B

JF - Journal of Physical Chemistry B

SN - 1520-6106

IS - 39

ER -