1epo
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| , resolution 2.0Å | |||||||
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| Ligands: | , , , | ||||||
| Activity: | Endothiapepsin, with EC number 3.4.23.22 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
DIRECT OBSERVATION BY X-RAY ANALYSIS OF THE TETRAHEDRAL "INTERMEDIATE" OF ASPARTIC PROTEINASES
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]. 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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