1epo
DIRECT OBSERVATION BY X-RAY ANALYSIS OF THE TETRAHEDRAL "INTERMEDIATE" OF ASPARTIC PROTEINASES
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OverviewOverview
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.
About this StructureAbout this Structure
1EPO is a Single protein structure of sequence from [1]. Active as Endothiapepsin, with EC number 3.4.23.22 Full crystallographic information is available from OCA.
ReferenceReference
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
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