Marcos, E and Crehuet, R and Bahar, I
(2011)
Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members.
PLoS Computational Biology, 7 (9).
ISSN 1553-734X
Abstract
Oligomerization is a functional requirement for many proteins. The interfacial interactions and the overall packing geometry of the individual monomers are viewed as important determinants of the thermodynamic stability and allosteric regulation of oligomers. The present study focuses on the role of the interfacial interactions and overall contact topology in the dynamic features acquired in the oligomeric state. To this aim, the collective dynamics of enzymes belonging to the amino acid kinase family both in dimeric and hexameric forms are examined by means of an elastic network model, and the softest collective motions (i.e., lowest frequency or global modes of motions) favored by the overall architecture are analyzed. Notably, the lowest-frequency modes accessible to the individual subunits in the absence of multimerization are conserved to a large extent in the oligomer, suggesting that the oligomer takes advantage of the intrinsic dynamics of the individual monomers. At the same time, oligomerization stiffens the interfacial regions of the monomers and confers new cooperative modes that exploit the rigid-body translational and rotational degrees of freedom of the intact monomers. The present study sheds light on the mechanism of cooperative inhibition of hexameric N-acetyl-L-glutamate kinase by arginine and on the allosteric regulation of UMP kinases. It also highlights the significance of the particular quaternary design in selectively determining the oligomer dynamics congruent with required ligand-binding and allosteric activities. © 2011 Marcos et al.
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Details
| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
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| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID  |
|---|
| Editor | Gilson, Michael | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
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| Date: |
1 September 2011 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS Computational Biology |
| Volume: |
7 |
| Number: |
9 |
| DOI or Unique Handle: |
10.1371/journal.pcbi.1002201 |
| Schools and Programs: |
School of Medicine > Computational and Systems Biology |
| Refereed: |
Yes |
| ISSN: |
1553-734X |
| MeSH Headings: |
Allosteric Regulation; Allosteric Site; Amino Acids--metabolism; Catalytic Domain; Computational Biology; Computer Simulation; Dimerization; Models, Molecular; Molecular Dynamics Simulation; Nucleoside-Phosphate Kinase--chemistry; Nucleoside-Phosphate Kinase--metabolism; Phosphotransferases--chemistry; Phosphotransferases--metabolism; Phosphotransferases (Carboxyl Group Acceptor)--chemistry; Phosphotransferases (Carboxyl Group Acceptor)--metabolism; Protein Binding; Protein Multimerization; Protein Structure, Quaternary; Substrate Specificity; Thermodynamics |
| Other ID: |
NLM PMC3182869 |
| PubMed Central ID: |
PMC3182869 |
| PubMed ID: |
21980279 |
| Date Deposited: |
05 Sep 2012 20:05 |
| Last Modified: |
17 Mar 2023 11:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/13901 |
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