Source:http://linkedlifedata.com/resource/pubmed/id/15229879
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2004-7-1
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| pubmed:abstractText |
A network of protein vibrations has recently been identified in the enzyme cyclophilin A (CypA) that is associated with its peptidyl-prolyl cis/trans isomerization activity of small peptide substrates. It has been suggested that this network may have a role in promoting the catalytic step during the isomerization reaction. This work presents the results from the characterization of this network during the isomerization of the Gly89-Pro90 peptide bond in the N-terminal domain of the capsid protein (CA(N)) from human immunodeficiency virus type 1 (HIV-1), which is a naturally occurring, biologically relevant protein substrate for CypA. A variety of computational and theoretical studies are utilized to investigate the protein dynamics of the CypA-CA(N) complex, at multiple time scales, during the isomerization step. The results provide insights into the detailed mechanism of isomerization and confirm the presence of previously reported network of protein vibrations coupled to the reaction. Conserved CypA residues at the complex interface and at positions distal to the interface form parts of this network. There is HIV-1 related medical interest in CypA; incorporation of CypA, complexed with the capsid protein, into the virion is required for the infectious activity of HIV-1. Interaction energy and dynamical cross-correlation calculations are used for a detailed investigation of the protein-protein interactions in the CypA-CA(N) complex. The results show that CA(N) residues His87-Ala-Gly-Pro-Ile-Ala92 form the majority of the interactions with CypA residues. New protein-protein interactions distal to the active site (CypA Arg148-CA(N) Gln95 and CypA Arg148-CA(N) Asn121) are also identified.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Aug
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| pubmed:issn |
1097-0134
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2004 Wiley-Liss, Inc.
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| pubmed:issnType |
Electronic
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| pubmed:day |
15
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| pubmed:volume |
56
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
449-63
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:15229879-Catalysis,
pubmed-meshheading:15229879-Catalytic Domain,
pubmed-meshheading:15229879-Computer Simulation,
pubmed-meshheading:15229879-Cyclophilin A,
pubmed-meshheading:15229879-HIV Core Protein p24,
pubmed-meshheading:15229879-HIV-1,
pubmed-meshheading:15229879-Hydrogen Bonding,
pubmed-meshheading:15229879-Hydrophobic and Hydrophilic Interactions,
pubmed-meshheading:15229879-Isomerism,
pubmed-meshheading:15229879-Models, Chemical,
pubmed-meshheading:15229879-Protein Conformation,
pubmed-meshheading:15229879-Protein Structure, Secondary,
pubmed-meshheading:15229879-Protein Structure, Tertiary,
pubmed-meshheading:15229879-Rotation,
pubmed-meshheading:15229879-Thermodynamics,
pubmed-meshheading:15229879-Vibration
|
| pubmed:year |
2004
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| pubmed:articleTitle |
Cis/trans isomerization in HIV-1 capsid protein catalyzed by cyclophilin A: insights from computational and theoretical studies.
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| pubmed:affiliation |
Computational Biology Institute and Computer Science and Mathematics Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee, USA. agarwalpk@ornl.gov
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|