Structure of sortase, the transpeptidase that anchors proteins to the cell wall of Staphylococcus aureus

Udayar Ilangovan, Hung Ton-That, Junji Iwahara, Olaf Schneewind, Robert T. Clubb

Research output: Contribution to journalArticlepeer-review

226 Scopus citations

Abstract

Surface proteins of Gram-positive bacteria play important roles during the pathogenesis of human infections and require sortase for anchoring to the cell-wall envelope. Sortase cleaves surface proteins at the LPXTG motif and catalyzes the formation of an amide bond between the carboxyl group of threonine (T) and the amino group of cell-wall crossbridges. The NMR structure of sortase reveals a unique β-barrel structure, in which the active-site sulfhydryl of cysteine-184 is poised for ionization by histidine-120, presumably enabling the resultant thiolate to attack the LPXTG peptide. Calcium binding near the active site stimulates catalysis, possibly by altering the conformation of a surface loop that recognizes newly translocated polypeptides. The structure suggests a mechanistic relationship to the papain/cathepsin proteases and should facilitate the design of new antiinfective agents.

Original languageEnglish (US)
Pages (from-to)6056-6061
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number11
DOIs
StatePublished - May 22 2001

ASJC Scopus subject areas

  • General

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