The crystal structure analysis of group B streptococcus sortase C1: A model for the "lid" movement upon substrate binding

Baldeep Khare, Zheng Qing Fu, I. Hsiu Huang, Ton That Hung, Sthanam V.L. Narayana

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

A unique feature of the class-C-type sortases, enzymes essential for Gram-positive pilus biogenesis, is the presence of a flexible "lid" anchored in the active site. However, the mechanistic details of the "lid" displacement, suggested to be a critical prelude for enzyme catalysis, are not yet known. This is partly due to the absence of enzyme-substrate and enzyme-inhibitor complex crystal structures. We have recently described the crystal structures of the Streptococcus agalactiae SAG2603 V/R sortase SrtC1 in two space groups (type II and type III) and that of its "lid" mutant and proposed a role of the "lid" as a protector of the active-site hydrophobic environment. Here, we report the crystal structures of SAG2603 V/R sortase C1 in a different space group (type I) and that of its complex with a small-molecule cysteine protease inhibitor. We observe that the catalytic Cys residue is covalently linked to the small-molecule inhibitor without lid displacement. However, the type I structure provides a view of the sortase SrtC1 lid displacement while having structural elements similar to a substrate sorting motif suitably positioned in the active site. We propose that these major conformational changes seen in the presence of a substrate mimic in the active site may represent universal features of class C sortase substrate recognition and enzyme activation.

Original languageEnglish
Pages (from-to)563-577
Number of pages15
JournalJournal of Molecular Biology
Volume414
Issue number4
DOIs
StatePublished - 9 Dec 2011

Keywords

  • blocked active site
  • cysteine protease
  • Gram-positive pili biogenesis
  • pilus-specific sortase
  • sorting motif

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