3BEU

Na+-Dependent Allostery Mediates Coagulation Factor Protease Active Site Selectivity

3BEU の概要

• エントリーDOI: 10.2210/pdb3beu/pdb
• 分子名称: Trypsin, SULFATE ION, BENZAMIDINE, ... (6 entities in total)
• 機能のキーワード: beta sheets, serine protease, hydrolase, zymogen
• 由来する生物種: Streptomyces griseus
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 48742.34

構造登録者

Page, M.J.,Carrell, C.J.,Di Cera, E. (登録日: 2007-11-20, 公開日: 2008-03-11, 最終更新日: 2024-10-16)

主引用文献

Page, M.J.,Carrell, C.J.,Di Cera, E.
Engineering protein allostery: 1.05 A resolution structure and enzymatic properties of a Na+-activated trypsin.
J.Mol.Biol., 378:666-672, 2008

PubMed Abstract: Some trypsin-like proteases are endowed with Na(+)-dependent allosteric enhancement of catalytic activity, but this important mechanism has been difficult to engineer in other members of the family. Replacement of 19 amino acids in Streptomyces griseus trypsin targeting the active site and the Na(+)-binding site were found necessary to generate efficient Na(+) activation. Remarkably, this property was linked to the acquisition of a new substrate selectivity profile similar to that of factor Xa, a Na(+)-activated protease involved in blood coagulation. The X-ray crystal structure of the mutant trypsin solved to 1.05 A resolution defines the engineered Na(+) site and active site loops in unprecedented detail. The results demonstrate that trypsin can be engineered into an efficient allosteric protease, and that Na(+) activation is interwoven with substrate selectivity in the trypsin scaffold.

PubMed: 18377928
DOI: 10.1016/j.jmb.2008.03.003

実験手法

X-RAY DIFFRACTION (1.05 Å)