1eed
From Proteopedia
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X-RAY CRYSTALLOGRAPHIC ANALYSIS OF INHIBITION OF ENDOTHIAPEPSIN BY CYCLOHEXYL RENIN INHIBITORS
Overview
The crystal structures of endothiapepsin, a fungal aspartic proteinase (EC, 3.4.23.6), cocrystallized with two oligopeptide renin inhibitors, PD125967, and PD125754, have been determined at 2.0-A resolution and refined to, R-factors of 0.143 and 0.153, respectively. These inhibitors, which are of, the hydroxyethylene and statine types, respectively, possess a, cyclohexylalanine side chain at P1 and have interesting functionalities at, the P3 position which, until now, have not been subjected to, crystallographic analysis. PD125967 has a bis(1-naphthylmethyl)acetyl, residue at P3, and PD125754 possesses a hydroxyethylene analogue of the, P3-P2 peptide bond for proteolytic stability. The structures reveal that, the S3 pocket accommodates one naphthyl ring with conformational changes, of the Asp 77 and Asp 114 side chains, the other naphthyl group residing, in the S4 region. The P3-P2 hydroxyethylene analogue of PD125754 forms a, hydrogen bond with the NH of Thr 219, thereby making the same interaction, with the enzyme as the equivalent peptide groups of all inhibitors studied, so far. The absence of side chains at the P2 and P1' positions of this, inhibitor allows water molecules to occupy the respective pockets in the, complex. The relative potencies of PD125967 and PD125754 for, endothiapepsin are consistent with the changes in solvent-accessible area, which take place on inhibitor binding.
About this Structure
1EED 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.
Reference
X-ray crystallographic analysis of inhibition of endothiapepsin by cyclohexyl renin inhibitors., Cooper J, Quail W, Frazao C, Foundling SI, Blundell TL, Humblet C, Lunney EA, Lowther WT, Dunn BM, Biochemistry. 1992 Sep 8;31(35):8142-50. PMID:1525155
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