4Q2K

Bovine alpha chymotrypsin bound to a cyclic peptide inhibitor, 5b

4Q2K の概要

• エントリーDOI: 10.2210/pdb4q2k/pdb
• 分子名称: Chymotrypsinogen A, (11S)-4,9-dioxo-N-[(2S)-1-oxo-3-phenylpropan-2-yl]-17,22-dioxa-10,30-diazatetracyclo[21.2.2.2~13,16~.1~5,8~]triaconta-1(25),5,7,13,15,23,26,28-octaene-11-carboxamide (3 entities in total)
• 機能のキーワード: chymotrypsin, protease, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Bos taurus (bovine)
• 細胞内の位置: Secreted, extracellular space: P00766
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 105174.93

構造登録者

Chan, H.Y.,Bruning, J.B.,Abell, A.D. (登録日: 2014-04-09, 公開日: 2014-07-23, 最終更新日: 2024-11-13)

主引用文献

Chua, K.C.,Pietsch, M.,Zhang, X.,Hautmann, S.,Chan, H.Y.,Bruning, J.B.,Gutschow, M.,Abell, A.D.
Macrocyclic protease inhibitors with reduced peptide character.
Angew.Chem.Int.Ed.Engl., 53:7828-7831, 2014

PubMed Abstract: There is a real need for simple structures that define a β-strand conformation, a secondary structure that is central to peptide-protein interactions. For example, protease substrates and inhibitors almost universally adopt this geometry on active site binding. A planar pyrrole is used to replace two amino acids of a peptide backbone to generate a simple macrocycle that retains the required geometry for active site binding. The resulting β-strand templates have reduced peptide character and provide potent protease inhibitors with the attachment of an appropriate amino aldehyde to the C-terminus. Picomolar inhibitors of cathepsin L and S are reported and the mode of binding of one example to the model protease chymotrypsin is defined by X-ray crystallography.

PubMed: 24903745
DOI: 10.1002/anie.201404301

実験手法

X-RAY DIFFRACTION (2.2 Å)