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Coupling between Catalytic Loop Motions and Enzyme Global Dynamics

Kurkcuoglu, Z and Bakan, A and Kocaman, D and Bahar, I and Doruker, P (2012) Coupling between Catalytic Loop Motions and Enzyme Global Dynamics. PLoS Computational Biology, 8 (9). ISSN 1553-734X

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Catalytic loop motions facilitate substrate recognition and binding in many enzymes. While these motions appear to be highly flexible, their functional significance suggests that structure-encoded preferences may play a role in selecting particular mechanisms of motions. We performed an extensive study on a set of enzymes to assess whether the collective/global dynamics, as predicted by elastic network models (ENMs), facilitates or even defines the local motions undergone by functional loops. Our dataset includes a total of 117 crystal structures for ten enzymes of different sizes and oligomerization states. Each enzyme contains a specific functional/catalytic loop (10-21 residues long) that closes over the active site during catalysis. Principal component analysis (PCA) of the available crystal structures (including apo and ligand-bound forms) for each enzyme revealed the dominant conformational changes taking place in these loops upon substrate binding. These experimentally observed loop reconfigurations are shown to be predominantly driven by energetically favored modes of motion intrinsically accessible to the enzyme in the absence of its substrate. The analysis suggests that robust global modes cooperatively defined by the overall enzyme architecture also entail local components that assist in suitable opening/closure of the catalytic loop over the active site. © 2012 Kurkcuoglu et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Kurkcuoglu, Z
Bakan, Aahb12@pitt.eduAHB12
Kocaman, D
Bahar, Iivet.bahar@stonybrook.eduBAHAR
Doruker, P
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 September 2012
Date Type: Publication
Journal or Publication Title: PLoS Computational Biology
Volume: 8
Number: 9
DOI or Unique Handle: 10.1371/journal.pcbi.1002705
Schools and Programs: School of Medicine > Computational and Systems Biology
Refereed: Yes
ISSN: 1553-734X
Other ID: NLM PMC3459879
PubMed Central ID: PMC3459879
PubMed ID: 23028297
Date Deposited: 22 Oct 2012 21:27
Last Modified: 17 Mar 2023 11:55


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