Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form
D-Scholarship @ Pitt Banner and Links to Homepage

On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm

Marcos, E and Crehuet, R and Bahar, I (2010) On the conservation of the slow conformational dynamics within the amino acid kinase family: NAGK the paradigm. PLoS Computational Biology, 6 (4). ISSN 1553-734X

[img]
Preview
 PDF
Published Version
Available under License : See the attached license file.
Download (1MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.
Download (1kB)

Abstract

N-Acetyl-L-Glutamate Kinase (NAGK) is the structural paradigm for examining the catalytic mechanisms and dynamics of amino acid kinase family members. Given that the slow conformational dynamics of the NAGK (at the microseconds time scale or slower) may be rate-limiting, it is of importance to assess the mechanisms of the most cooperative modes of motion intrinsically accessible to this enzyme. Here, we present the results from normal mode analysis using an elastic network model representation, which shows that the conformational mechanisms for substrate binding by NAGK strongly correlate with the intrinsic dynamics of the enzyme in the unbound form. We further analyzed the potential mechanisms of allosteric signalling within NAGK using a Markov model for network communication. Comparative analysis of the dynamics of family members strongly suggests that the low-frequency modes of motion and the associated intramolecular couplings that establish signal transduction are highly conserved among family members, in support of the paradigm sequence→structure→dynamics→function © 2010 Marcos et al.

Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Marcos, E
Crehuet, R
Bahar, Iivet.bahar@stonybrook.eduBAHAR
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorLevitt, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 1 April 2010
Date Type: Publication
Journal or Publication Title: PLoS Computational Biology
Volume: 6
Number: 4
DOI or Unique Handle: 10.1371/journal.pcbi.1000738
Schools and Programs: School of Medicine > Computational Biology
Refereed: Yes
ISSN: 1553-734X
MeSH Headings: Allosteric Regulation; Anisotropy; Catalytic Domain; Computational Biology--methods; Markov Chains; Molecular Dynamics Simulation; Normal Distribution; Phosphotransferases (Carboxyl Group Acceptor)--chemistry; Phosphotransferases (Carboxyl Group Acceptor)--metabolism; Signal Transduction; Structure-Activity Relationship
Other ID: NLM PMC2851564
PubMed Central ID: PMC2851564
PubMed ID: 20386738
Date Deposited: 03 Aug 2012 18:53
Last Modified: 17 Mar 2023 11:55
URI: http://d-scholarship.pitt.edu/id/eprint/13347

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com

Actions (login required)

View Item View Item