2WTS

Crystal structure of sortase C-1 (SrtC-1) mutant H131D from S. pneumoniae

2WTS の概要

• エントリーDOI: 10.2210/pdb2wts/pdb
• 関連するPDBエントリー: 2W1J
• 分子名称: PUTATIVE SORTASE, GLYCEROL, ALANINE, ... (4 entities in total)
• 機能のキーワード: transferase, pili, pathogenicity
• 由来する生物種: STREPTOCOCCUS PNEUMONIAE
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 47945.16

構造登録者

Manzano, C.,Izore, T.,Job, V.,DiGuilmi, A.M.,Dessen, A. (登録日: 2009-09-21, 公開日: 2010-09-01, 最終更新日: 2023-12-20)

主引用文献

Manzano, C.,Izore, T.,Job, V.,Di Guilmi, A.M.,Dessen, A.
Sortase Activity is Controlled by a Flexible Lid in the Pilus Biogenesis Mechanism of Gram-Positive Pathogens.
Biochemistry, 48:10549-, 2009

PubMed Abstract: Pili are surface-linked virulence factors that play key roles in infection establishment in a variety of pathogenic species. In Gram-positive pathogens, pilus formation requires the action of sortases, dedicated transpeptidases that covalently associate pilus building blocks. In Streptococcus pneumoniae, a major human pathogen, all genes required for pilus formation are harbored in a single pathogenicity islet which encodes three structural proteins (RrgA, RrgB, RrgC) and three sortases (SrtC-1, SrtC-2, SrtC-3). RrgB forms the backbone of the streptococcal pilus, to which minor pilins RrgA and RrgC are covalently associated. SrtC-1 is the main sortase involved in polymerization of the RrgB fiber and displays a lid which encapsulates the active site, a feature present in all pilus-related sortases. In this work, we show that catalysis by SrtC-1 proceeds through a catalytic triad constituted of His, Arg, and Cys and that lid instability affects protein fold and catalysis. In addition, we show by thermal shift analysis that lid flexibility can be stabilized by the addition of substrate-like peptides, a feature shared by other periplasmic transpeptidases. We also report the characterization of a trapped acyl-enzyme intermediate formed between SrtC-1 and RrgB. The presence of lid-encapsulated sortases in the pilus biogenesis systems in many Gram-positive pathogens points to a common mechanism of substrate recognition and catalysis that should be taken into consideration in the development of sortase inhibitors.

PubMed: 19810750
DOI: 10.1021/BI901261Y

実験手法

X-RAY DIFFRACTION (1.3 Å)