title: Structure of sortase, the transpeptidase that anchors proteins to the cell wall of Staphylococcus aureus.
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 beta-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.
authors.affiliation: Department of Chemistry and Biochemistry and University of California at Los Angeles, CA 90095, USA.
authors.forename: U
authors.initials: U
authors.lastname: Ilangovan
authors.forename: H
authors.initials: H
authors.lastname: Ton-That
authors.forename: J
authors.initials: J
authors.lastname: Iwahara
authors.forename: O
authors.initials: O
authors.lastname: Schneewind
authors.forename: R T
authors.initials: RT
authors.lastname: Clubb
mesh_terms: D019881:Aminoacyltransferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D020134:Catalytic Domain; D002413:Cations, Divalent; D002473:Cell Wall / Q000378:metabolism; D003546:Cysteine Endopeptidases; D010458:Peptidyl Transferases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013211:Staphylococcus aureus / Q000201:enzymology
chemical_list: D001426:Bacterial Proteins; D002413:Cations, Divalent; D019881:Aminoacyltransferases; C120542:sortase A; D010458:Peptidyl Transferases; D003546:Cysteine Endopeptidases; D002118:Calcium