2AIM

CRUZAIN INHIBITED WITH BENZOYL-ARGININE-ALANINE-FLUOROMETHYLKETONE

2AIM の概要

• エントリーDOI: 10.2210/pdb2aim/pdb
• 分子名称: CRUZAIN, BENZOYL-ARGININE-ALANINE-FLUORO-METHYL KETONE (3 entities in total)
• 機能のキーワード: cysteine protease, trypanosoma cruzi, proteinase, protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Trypanosoma cruzi
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23112.58

構造登録者

Gillmor, S.A.,Fletterick, R.J. (登録日: 1997-04-21, 公開日: 1997-10-22, 最終更新日: 2024-10-30)

主引用文献

Gillmor, S.A.,Craik, C.S.,Fletterick, R.J.
Structural determinants of specificity in the cysteine protease cruzain.
Protein Sci., 6:1603-1611, 1997

PubMed Abstract: The structure of cruzain, an essential protease from the parasite Trypanosoma cruzi, was determined by X-ray crystallography bound to two different covalent inhibitors. The cruzain S2 specificity pocket is able to productively bind both arginine and phenylalanine residues. The structures of cruzain bound to benzoyl-Arg-Ala-fluoromethyl ketone and benzoyl-Tyr-Ala-fluoromethyl ketone at 2.2 and 2.1 A, respectively, show a pH-dependent specificity switch. Glu 205 adjusts to restructure the S2 specificity pocket, conferring right binding to both hydrophobic and basic residues. Kinetic analysis of activated peptide substrates shows that substrates placing hydrophobic residues in the specificity pocket are cleaved at a broader pH range than hydrophilic substrates. These results demonstrate how cruzain binds both basic and hydrophobic residues and could be important for in vivo regulation of cruzain activity.

PubMed: 9260273

実験手法

X-RAY DIFFRACTION (2.2 Å)