Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members.
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...
Main Authors: | , , |
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פורמט: | Article |
שפה: | English |
יצא לאור: |
Public Library of Science (PLoS)
2011-09-01
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סדרה: | PLoS Computational Biology |
גישה מקוונת: | http://europepmc.org/articles/PMC3182869?pdf=render |
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author | Enrique Marcos Ramon Crehuet Ivet Bahar |
author_facet | Enrique Marcos Ramon Crehuet Ivet Bahar |
author_sort | Enrique Marcos |
collection | DOAJ |
description | 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. |
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id | doaj.art-2e738338b3044b51a18c8fa37369688c |
institution | Directory Open Access Journal |
issn | 1553-734X 1553-7358 |
language | English |
last_indexed | 2024-12-12T18:37:43Z |
publishDate | 2011-09-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS Computational Biology |
spelling | doaj.art-2e738338b3044b51a18c8fa37369688c2022-12-22T00:15:44ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582011-09-0179e100220110.1371/journal.pcbi.1002201Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members.Enrique MarcosRamon CrehuetIvet BaharOligomerization 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.http://europepmc.org/articles/PMC3182869?pdf=render |
spellingShingle | Enrique Marcos Ramon Crehuet Ivet Bahar Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members. PLoS Computational Biology |
title | Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members. |
title_full | Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members. |
title_fullStr | Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members. |
title_full_unstemmed | Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members. |
title_short | Changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members. |
title_sort | changes in dynamics upon oligomerization regulate substrate binding and allostery in amino acid kinase family members |
url | http://europepmc.org/articles/PMC3182869?pdf=render |
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