2CV3

Crystal structure of porcine pancreatic elastase complexed with a macroclyclic peptide inhibitor

2CV3 の概要

• エントリーDOI: 10.2210/pdb2cv3/pdb
• 関連するBIRD辞書のPRD_ID: PRD_000571
• 分子名称: Elastase 1, Inhibitor FR901451 (3 entities in total)
• 機能のキーワード: protein-inhibitor interaction, macrocyclic peptide, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Sus scrofa (pig); 詳細
• 細胞内の位置: Secreted: P00772
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27254.42

構造登録者

Kinoshita, T.,Tada, T.,Kitatani, T. (登録日: 2005-05-31, 公開日: 2006-05-16, 最終更新日: 2024-10-23)

主引用文献

Kinoshita, T.,Kitatani, T.,Warizaya, M.,Tada, T.
Structure of the complex of porcine pancreatic elastase with a trimacrocyclic peptide inhibitor FR901451
Acta Crystallogr.,Sect.F, 61:808-811, 2005

PubMed Abstract: Porcine pancreatic elastase (PPE) resembles the attractive drug target leukocyte elastase, which has the ability to degrade connective tissue in the body. The crystal structure of PPE complexed with a novel trimacrocyclic peptide inhibitor, FR901451, was solved at 1.9 A resolution. The inhibitor occupied the subsites S3 through S3' of PPE and induced conformational changes in the side chains of Arg64 and Arg226, which are located at the edges of the substrate-binding cleft. Structural comparison of five PPE-inhibitor complexes, including the FR901451 complex and non-ligated PPE, reveals that the residues forming the S2, S1, S1' and S2' subsites in the cleft are rigid, but the two arginine residues playing a part in the S3 and S3' subsites are flexible. Structural comparison of PPE with human leukocyte elastase (HLE) implies that the inhibitor binds to HLE in a similar manner to the FR901451-PPE complex. This structural insight may help in the design of potent elastase inhibitors.

PubMed: 16511165
DOI: 10.1107/S1744309105026047

実験手法

X-RAY DIFFRACTION (1.9 Å)