4H4F

Crystal structure of human chymotrypsin C (CTRC) bound to inhibitor eglin c from Hirudo medicinalis

4H4F の概要

• エントリーDOI: 10.2210/pdb4h4f/pdb
• 分子名称: Chymotrypsin-C, Eglin C, PHOSPHATE ION, ... (5 entities in total)
• 機能のキーワード: serine protease, protease inhibitor, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 37441.99

構造登録者

Batra, J.,Soares, A.S.,Radisky, E.S. (登録日: 2012-09-17, 公開日: 2013-02-27, 最終更新日: 2024-10-30)

主引用文献

Batra, J.,Szabo, A.,Caulfield, T.R.,Soares, A.S.,Sahin-Toth, M.,Radisky, E.S.
Long-range Electrostatic Complementarity Governs Substrate Recognition by Human Chymotrypsin C, a Key Regulator of Digestive Enzyme Activation.
J.Biol.Chem., 288:9848-9859, 2013

PubMed Abstract: Human chymotrypsin C (CTRC) is a pancreatic serine protease that regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. In cleaving these regulatory sites, which are characterized by multiple flanking acidic residues, CTRC shows substrate specificity that is distinct from that of other isoforms of chymotrypsin and elastase. Here, we report the first crystal structure of active CTRC, determined at 1.9-Å resolution, revealing the structural basis for binding specificity. The structure shows human CTRC bound to the small protein protease inhibitor eglin c, which binds in a substrate-like manner filling the S6-S5' subsites of the substrate binding cleft. Significant binding affinity derives from burial of preferred hydrophobic residues at the P1, P4, and P2' positions of CTRC, although acidic P2' residues can also be accommodated by formation of an interfacial salt bridge. Acidic residues may also be specifically accommodated in the P6 position. The most unique structural feature of CTRC is a ring of intense positive electrostatic surface potential surrounding the primarily hydrophobic substrate binding site. Our results indicate that long-range electrostatic attraction toward substrates of concentrated negative charge governs substrate discrimination, which explains CTRC selectivity in regulating active digestive enzyme levels.

PubMed: 23430245
DOI: 10.1074/jbc.M113.457382

実験手法

X-RAY DIFFRACTION (1.9 Å)