4D8B

High resolution structure of monomeric S. progenies SpeB reveals role of glycine-rich active site loop

4D8B の概要

• エントリーDOI: 10.2210/pdb4d8b/pdb
• 関連するPDBエントリー: 1DKI 2JTC 2UZJ 4D8E 4D8I
• 分子名称: Streptopain, NITRATE ION (3 entities in total)
• 機能のキーワード: papain fold, cysteine protease, secreted, hydrolase
• 由来する生物種: Streptococcus pyogenes
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28743.70

構造登録者

Gonzalez, G.E.,Wolan, D.W. (登録日: 2012-01-10, 公開日: 2012-06-06, 最終更新日: 2024-02-28)

主引用文献

Gonzalez-Paez, G.E.,Wolan, D.W.
Ultrahigh and High Resolution Structures and Mutational Analysis of Monomeric Streptococcus pyogenes SpeB Reveal a Functional Role for the Glycine-rich C-terminal Loop.
J.Biol.Chem., 287:24412-24426, 2012

PubMed Abstract: Cysteine protease SpeB is secreted from Streptococcus pyogenes and has been studied as a potential virulence factor since its identification almost 70 years ago. Here, we report the crystal structures of apo mature SpeB to 1.06 Å resolution as well as complexes with the general cysteine protease inhibitor trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane and a novel substrate mimetic peptide inhibitor. These structures uncover conformational changes associated with maturation of SpeB from the inactive zymogen to its active form and identify the residues required for substrate binding. With the use of a newly developed fluorogenic tripeptide substrate to measure SpeB activity, we determined IC(50) values for trans-epoxysuccinyl-l-leucylamido(4-guanidino)butane and our new peptide inhibitor and the effects of mutations within the C-terminal active site loop. The structures and mutational analysis suggest that the conformational movements of the glycine-rich C-terminal loop are important for the recognition and recruitment of biological substrates and release of hydrolyzed products.

PubMed: 22645124
DOI: 10.1074/jbc.M112.361576

実験手法

X-RAY DIFFRACTION (1.058 Å)