4GUX

Crystal structure of trypsin:MCoTi-II complex

4GUX の概要

• エントリーDOI: 10.2210/pdb4gux/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000750
• 分子名称: Cationic trypsin, Trypsin inhibitor 2, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: cyclotide, cyclic peptide, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Bos taurus (bovine,cow,domestic cattle,domestic cow); 詳細
• 細胞内の位置: Secreted, extracellular space: P00760; Secreted: P82409
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 88106.03

構造登録者

King, G.J.,Daly, N.L.,Thorstholm, L.,Greenwood, K.P.,Rosengren, K.J.,Heras, B.,Craik, D.J.,Martin, J.L. (登録日: 2012-08-30, 公開日: 2013-09-04, 最終更新日: 2024-11-06)

主引用文献

Daly, N.L.,Thorstholm, L.,Greenwood, K.P.,King, G.J.,Rosengren, K.J.,Heras, B.,Martin, J.L.,Craik, D.J.
Structural insights into the role of the cyclic backbone in a squash trypsin inhibitor
J.Biol.Chem., 288:36141-36148, 2013

PubMed Abstract: MCoTI-II is a head-to-tail cyclic peptide with potent trypsin inhibitory activity and, on the basis of its exceptional proteolytic stability, is a valuable template for the design of novel drug leads. Insights into inhibitor dynamics and interactions with biological targets are critical for drug design studies, particularly for protease targets. Here, we show that the cyclization and active site loops of MCoTI-II are flexible in solution, but when bound to trypsin, the active site loop converges to a single well defined conformation. This finding of reduced flexibility on binding is in contrast to a recent study on the homologous peptide MCoTI-I, which suggested that regions of the peptide are more flexible upon binding to trypsin. We provide a possible explanation for this discrepancy based on degradation of the complex over time. Our study also unexpectedly shows that the cyclization loop, not present in acyclic homologues, facilitates potent trypsin inhibitory activity by engaging in direct binding interactions with trypsin.

PubMed: 24169696
DOI: 10.1074/jbc.M113.528240

実験手法

X-RAY DIFFRACTION (1.803 Å)