Structural highlights
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We report the X-ray analysis at 2.0 A resolution for crystals of the aspartic proteinase endothiapepsin (EC 3.4.23.6) complexed with a potent difluorostatone-containing tripeptide renin inhibitor (CP-81,282). The scissile bond surrogate, an electrophilic ketone, is hydrated in the complex. The pro-(R) (statine-like) hydroxyl of the tetrahedral carbonyl hydrate is hydrogen-bonded to both active-site aspartates 32 and 215 in the position occupied by a water in the native enzyme. The second hydroxyl oxygen of the hydrate is hydrogen-bonded only to the outer oxygen of Asp 32. These experimental data provide a basis for a model of the tetrahedral intermediate in aspartic proteinase-mediated cleavage of the amide bond. This indicates a mechanism in which Asp 32 is the proton donor and Asp 215 carboxylate polarizes a bound water for nucleophilic attack. The mechanism involves a carboxylate (Asp 32) that is stabilized by extensive hydrogen bonding, rather than an oxyanion derivative of the peptide as in serine proteinase catalysis.
Direct observation by X-ray analysis of the tetrahedral "intermediate" of aspartic proteinases.,Veerapandian B, Cooper JB, Sali A, Blundell TL, Rosati RL, Dominy BW, Damon DB, Hoover DJ Protein Sci. 1992 Mar;1(3):322-8. PMID:1304340[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Veerapandian B, Cooper JB, Sali A, Blundell TL, Rosati RL, Dominy BW, Damon DB, Hoover DJ. Direct observation by X-ray analysis of the tetrahedral "intermediate" of aspartic proteinases. Protein Sci. 1992 Mar;1(3):322-8. PMID:1304340
