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Science 10 March 1989:
Vol. 243. no. 4896, pp. 1346 - 1351
DOI: 10.1126/science.2493678
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Articles

Science, Vol 243, Issue 4896, 1346-1351
Copyright © 1989 by American Association for the Advancement of Science

articles

Structure of recombinant human renin, a target for cardiovascular-active drugs, at 2.5 A resolution

AR Sielecki, K Hayakawa, M Fujinaga, ME Murphy, M Fraser, AK Muir, CT Carilli, JA Lewicki, JD Baxter, and MN James

Department of Biochemistry, University of Alberta, Edmonton, Canada.

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.


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Renin, Prorenin and the Putative (Pro)renin Receptor.
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Crystallographic Studies on the Binding Modes of P(2)-P(3) Butanediamide Renin Inhibitors.
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