2ER0

X-RAY STUDIES OF ASPARTIC PROTEINASE-STATINE INHIBITOR COMPLEXES

Summary for 2ER0

• Entry DOI: 10.2210/pdb2er0/pdb
• Descriptor: ENDOTHIAPEPSIN, L364,099 (2 entities in total)
• Functional Keywords: acid proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Cryphonectria parasitica (chestnut blight fungus)
• Total number of polymer chains: 2
• Total formula weight: 34894.18

Authors

Cooper, J.B.,Foundling, S.I.,Boger, J.,Blundell, T.L. (deposition date: 1990-10-20, release date: 1991-01-15, Last modification date: 2024-11-06)

Primary citation

Cooper, J.B.,Foundling, S.I.,Blundell, T.L.,Boger, J.,Jupp, R.A.,Kay, J.
X-ray studies of aspartic proteinase-statine inhibitor complexes.
Biochemistry, 28:8596-8603, 1989

PubMed Abstract: The conformation of a statine-containing renin inhibitor complexed with the aspartic proteinase from the fungus Endothia parasitica (EC 3.4.23.6) has been determined by X-ray diffraction at 2.2-A resolution (R = 0.17). We describe the structure of the complex at high resolution and compare this with a 3.0-A resolution analysis of a bound inhibitor, L-364,099, containing a cyclohexylalanine analogue of statine. The inhibitors bind in extended conformations in the long active-site cleft, and the hydroxyl of the transition-state analogue, statine, interacts strongly with the catalytic aspartates via hydrogen bonds to the essential carboxyl groups. This work provides a detailed structural analysis of the role of statine in peptide inhibitors. It shows conclusively that statine should be considered a dipeptide analogue (occupying P1 to P1') despite lacking the equivalent of a P1' side chain, although other inhibitor residues (especially P2) may compensate by interacting at the unoccupied S1' specificity subsite.

PubMed: 2690945
DOI: 10.1021/bi00447a049

Experimental method

X-RAY DIFFRACTION (3 Å)