4BD9

Structure of the complex between SmCI and human carboxypeptidase A4

4BD9 の概要

• エントリーDOI: 10.2210/pdb4bd9/pdb
• 関連するPDBエントリー: 2BO9 2BOA 4A94
• 分子名称: CARBOXYPEPTIDASE A4, CARBOXYPEPTIDASE INHIBITOR SMCI, ZINC ION, ... (4 entities in total)
• 機能のキーワード: hydrolase-hydrolase inhibitor complex, serine protease inhibitor, hydrolase/hydrolase inhibitor
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Secreted (By similarity): Q9UI42
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53541.04

構造登録者

Alonso-del-Ribero, M.,Reytor, M.L.,Trejo, S.A.,Chavez, M.A.,Aviles, F.X.,Reverter, D. (登録日: 2012-10-05, 公開日: 2013-07-17, 最終更新日: 2024-11-13)

主引用文献

Alonso Del Rivero, M.,Reytor, M.L.,Trejo, S.A.,Chavez, M.A.,Aviles, F.X.,Reverter, D.
A Noncanonical Mechanism of Carboxypeptidase Inhibition Revealed by the Crystal Structure of the Tri-Kunitz Smci in Complex with Human Cpa4.
Structure, 21:1118-, 2013

PubMed Abstract: The crystal structure of SmCI (Sabellastarte magnifica carboxypeptidase inhibitor) has been determined in complex with human carboxypeptidase A4 (hCPA4). SmCI is composed by three BPTI/Kunitz domains, each one displaying high structural homology and functionality with serine protease inhibitors. Moreover, SmCI possesses a distinctive capability to inhibit metallo-carboxypeptidases, constituting a bifunctional metallocarboxy- and serine protease inhibitor. The structure of the 1:1 complex of SmCI with hCPA4 reveals a noncanonical mechanism of carboxypeptidase inhibition, which surprisingly occurs mainly via the N-terminal segment, which penetrates into the active site groove of the enzyme. Mutagenesis and biochemical analysis confirm the major role of the N-terminal segment in the inhibition of carboxypeptidases. SmCI represents a tri-Kunitz serine protease inhibitor adapted to inhibit metallo-carboxypeptidases and discloses an unusual mechanism of inhibition by the N-terminal segment, emulating the "classical" C-terminal substrate-like inhibition.

PubMed: 23746805
DOI: 10.1016/J.STR.2013.04.021

実験手法

X-RAY DIFFRACTION (2.2 Å)