Publication Date:
1989-03-10
Description:
The x-ray crystal structure of recombinant human renin has been determined. Molecular dynamics techniques that included crystallographic data as a restraint were used to improve an initial model based on porcine pepsinogen. The present agreement factor for data from 8.0 to 2.5 angstroms (A) is 0.236. Some of the surface loops are poorly determined, and these disordered regions border a 30 A wide solvent channel. Comparison of renin with other aspartyl proteinases shows that, although the structural cores and active sites are highly conserved, surface residues, some of which are critical for specificity, vary greatly (up to 10A). Knowledge of the actual structure, as opposed to the use of models based on related enzymes, should facilitate the design of renin inhibitors.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sielecki, A R -- Hayakawa, K -- Fujinaga, M -- Murphy, M E -- Fraser, M -- Muir, A K -- Carilli, C T -- Lewicki, J A -- Baxter, J D -- James, M N -- New York, N.Y. -- Science. 1989 Mar 10;243(4896):1346-51.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, University of Alberta, Edmonton, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2493678" target="_blank"〉PubMed〈/a〉
Keywords:
Aspartic Acid Endopeptidases
;
Cardiovascular Agents/pharmacology
;
Endopeptidases/metabolism
;
Humans
;
Models, Molecular
;
Pepsin A/metabolism
;
Protein Conformation
;
*Recombinant Proteins/metabolism
;
*Renin/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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