2BB4

Porcine pancreatic elastase complexed with beta-casomorphin-7 and Asp-Phe at pH 5.0

2BB4 の概要

• エントリーDOI: 10.2210/pdb2bb4/pdb
• 関連するPDBエントリー: 1HAX 1HAY 1HAZ 1QIX 2BD2 2BD3 2BD4 2BD5 2BD6 2BD7 2BD8 2BD9 2BDA 2BDB 2BDC
• 分子名称: beta-casomorphin-7, Chymotrypsin-like elastase family member 1, CALCIUM ION, ... (5 entities in total)
• 機能のキーワード: serine proteinase, hydrolase
• 由来する生物種: Sus scrofa (pig); 詳細
• 細胞内の位置: Secreted: 2BB4
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 27190.43

構造登録者

Liu, B.,Schofield, C.J.,Wilmouth, R.C. (登録日: 2005-10-17, 公開日: 2006-05-30, 最終更新日: 2024-10-30)

主引用文献

Liu, B.,Schofield, C.J.,Wilmouth, R.C.
Structural analyses on intermediates in serine protease catalysis
J.Biol.Chem., 281:24024-24035, 2006

PubMed Abstract: Although the subject of many studies, detailed structural information on aspects of the catalytic cycle of serine proteases is lacking. Crystallographic analyses were performed in which an acyl-enzyme complex, formed from elastase and a peptide, was reacted with a series of nucleophilic dipeptides. Multiple analyses led to electron density maps consistent with the formation of a tetrahedral species. In certain cases, apparent peptide bond formation at the active site was observed, and the electron density maps suggested production of a cis-amide rather than a trans-amide. Evidence for a cis-amide configuration was also observed in the noncovalent complex between elastase and an alpha1-antitrypsin-derived tetrapeptide. Although there are caveats on the relevance of the crystallographic data to solution catalysis, the results enable detailed proposals for the pathway of the acylation step to be made. At least in some cases, it is proposed that the alcohol of Ser-195 may preferentially attack the carbonyl of the cis-amide form of the substrate, in a stereoelectronically favored manner, to give a tetrahedral oxyanion intermediate, which undergoes N-inversion and/or C-N bond rotation to enable protonation of the leaving group nitrogen. The mechanistic proposals may have consequences for protease inhibition, in particular for the design of high energy intermediate analogues.

PubMed: 16754679
DOI: 10.1074/jbc.M600495200

実験手法

X-RAY DIFFRACTION (1.6 Å)