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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
1989-8-8
|
| pubmed:abstractText |
Structural fluctuations of the apoenzyme form of carboxypeptidase A (EC 3.4.12.2) have been evaluated on the basis of molecular dynamics. The Konnert-Hendrickson refined coordinates of 2437 non-hydrogen atoms of the 307 amino acid residues derived from the X-ray structure of the holoenzyme served as the molecular model together with 548 calculated polar hydrogen atoms and 25 buried solvent molecules. Molecular dynamics simulations were carried out at 277 K, and the averaged structural properties of the protein were evaluated for the terminal 20 picosecond portion of a 48 picosecond trajectory. The average atomic displacement from the initial X-ray structure was 2.49 A for all atoms and 1.79 A for C alpha atoms. The average root-mean-square (r.m.s.) fluctuation of all atoms was 0.67 A as compared to 0.54 A evaluated from the X-ray-defined temperature factors. Corresponding r.m.s. fluctuations for backbone atoms were 0.56 A by molecular dynamics and 0.49 A by X-ray. On the basis of these molecular dynamics studies of the isolated molecule, it is shown that amino acid residues corresponding to intermolecular contact sites of the crystalline enzyme are associated with high amplitude motion. All eight segments of alpha-helix and eight regions of beta-strand were well preserved except for unwinding of the five C-terminal residues of the alpha-helix 112-122 that form part of an intermolecular contact in the crystal. Four regions of beta-strand and one alpha-helix with residues adjacent to or in the active site constitute a core of constant secondary structure and are shown not to change in relative orientation to each other during the course of the trajectory. The absence of the zinc ion does not markedly influence the stereochemical relationships of active site residues in the dynamically averaged protein. The extent of motional fluctuations of each of the subsites of substrate recognition in the active site has been evaluated. Active site residues responsible for specificity of substrate binding or splitting of the scissile bond exhibit low simulated motion. In contrast, residues in more distal sites of substrate recognition exhibit markedly greater motional fluctuations. This differential extent of dynamical motion is related to structural requirements of substrate hydrolysis.
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| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
0022-2836
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
5
|
| pubmed:volume |
207
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
201-16
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:2738924-Amino Acid Sequence,
pubmed-meshheading:2738924-Animals,
pubmed-meshheading:2738924-Binding Sites,
pubmed-meshheading:2738924-Carboxypeptidases,
pubmed-meshheading:2738924-Carboxypeptidases A,
pubmed-meshheading:2738924-Models, Molecular,
pubmed-meshheading:2738924-Models, Structural,
pubmed-meshheading:2738924-Protein Conformation,
pubmed-meshheading:2738924-Time Factors,
pubmed-meshheading:2738924-X-Ray Diffraction
|
| pubmed:year |
1989
|
| pubmed:articleTitle |
Dynamical structure of carboxypeptidase A.
|
| pubmed:affiliation |
Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|