Structure of Sortase, The Transpeptidase That Anchors Proteins to the Cell Wall of Staphylococcus aureus

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 11; pp. 6056 - 6061
• Main Authors: Ilangovan, Udayar, Ton-That, Hung, Iwahara, Junji, Schneewind, Olaf, Clubb, Robert T.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 22-05-2001; National Acad Sciences; The National Academy of Sciences
• Subjects: Active sites; Amides; Amino acids; Aminoacyltransferases - chemistry; Aminoacyltransferases - genetics; Aminoacyltransferases - metabolism; Bacteria; Bacterial Proteins - metabolism; Biochemistry; Biological Sciences; Calcium; Calcium - metabolism; Catalysis; Catalytic Domain; Cations, Divalent; Cell Wall - metabolism; Cell walls; Cells; Cysteine Endopeptidases; Enzymes; Infections; Membrane proteins; Peptidyl Transferases - chemistry; Peptidyl Transferases - genetics; Peptidyl Transferases - metabolism; protein anchors; Protein Binding; Protein Structure, Secondary; Proteins; Protons; sortase; Staphylococcus aureus; Staphylococcus aureus - enzymology; transpeptidase
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.101064198

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.