1EPO

ENDOTHIA ASPARTIC PROTEINASE (ENDOTHIAPEPSIN) COMPLEXED WITH CP-81,282 (MOR PHE NLE CHF NME)

1EPO の概要

• エントリーDOI: 10.2210/pdb1epo/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000416
• 分子名称: ENDOTHIAPEPSIN, N-(morpholin-4-ylcarbonyl)-L-phenylalanyl-N-[(1R)-1-(cyclohexylmethyl)-3,3-difluoro-2,2-dihydroxy-4-(methylamino)-4-oxobutyl]-L-norleucinamide (3 entities in total)
• 機能のキーワード: acid proteinase, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Cryphonectria parasitica (chestnut blight fungus)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34467.61

構造登録者

Veerapandian, B.,Cooper, J.B.,Blundell, T.L. (登録日: 1994-07-27, 公開日: 1994-12-20, 最終更新日: 2024-10-23)

主引用文献

Veerapandian, B.,Cooper, J.B.,Sali, A.,Blundell, T.L.,Rosati, R.L.,Dominy, B.W.,Damon, D.B.,Hoover, D.J.
Direct observation by X-ray analysis of the tetrahedral intermediate of aspartic proteinases.
Protein Sci., 1:322-328, 1992

PubMed Abstract: 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.

PubMed: 1304340

実験手法

X-RAY DIFFRACTION (2 Å)