A network of conserved interactions regulates the allosteric signal in a glutamine amidotransferase.

Abstract:

:We have combined equilibrium and steered molecular dynamics (SMD) simulations with principal component and correlation analyses to probe the mechanism of allosteric regulation in imidazole glycerol phosphate (IGP) synthase. An evolutionary analysis of IGP synthase revealed a conserved network of interactions leading from the effector binding site to the glutaminase active site, forming conserved communication pathways between the remote active sites. SMD simulations of the undocking of the ribonucleotide effector N1-[(5'-phosphoribulosyl)-formino]-5'-aminoimidazole carboxamide ribonucleotide (PRFAR) resulted in a large scale hinge-opening motion at the interface. Principal component analysis and a correlation analysis of the equilibration protein motion indicate that the dynamics involved in the allosteric transition are mediated by coupled motion between sites that are more than 25 A apart. Furthermore, conserved residues at the substrate-binding site, within the barrel, and at the interface were found to exhibit highly correlated motion during the allosteric transition. The coupled motion between PRFAR unbinding and the directed opening of the interface is interpreted in combination with kinetic assays for the wild-type and mutant systems to develop a model of allosteric regulation in IGP synthase that is monitored and investigated with atomic resolution.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Amaro RE,Sethi A,Myers RS,Davisson VJ,Luthey-Schulten ZA

doi

10.1021/bi061708e

subject

Has Abstract

pub_date

2007-02-27 00:00:00

pages

2156-73

issue

8

eissn

0006-2960

issn

1520-4995

journal_volume

46

pub_type

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