The Structure of Sortase B, a Cysteine Transpeptidase that Tethers Surface Protein to the Staphylococcus aureus Cell Wall
Abstract
Many surface proteins of Gram-positive bacteria, which play important roles during the pathogenesis of human infections, are anchored to the cell wall envelope by a mechanism requiring sortases. Sortase B, a cysteine transpeptidase from Staphylococcus aureus, cleaves the C-terminal sorting signal of IsdC at the NPQTN motif and tethers the polypeptide to the pentaglycine cell wall cross-bridge. During catalysis, the active site cysteine of sortase and the cleaved substrate form an acyl intermediate, which is then resolved by the amino group of pentaglycine cross-bridges. We report here the crystal structures of SrtB_(ΔN30) in complex with two active site inhibitors, MTSET and E64, and with the cell wall substrate analog tripleglycine. These structures reveal, for the first time, the active site disposition and the unique Cys-Arg catalytic machinery of the cysteine transpeptidase, and they also provide useful information for the future design of anti-infective agents against sortases.
Additional Information
© 2004 Cell Press. Published by Elsevier. Under an Elsevier user license. Received 14 July 2003, Revised 8 September 2003, Accepted 16 September 2003, Available online 16 January 2004. This work is partially supported by funding from NASA to S.V.L.N. We thank Prof. Ramarao Chodavarapu and Prof. Charles Craik for their constructive critique of this manuscript and Dr. Mike Carson for help in preparing figures. Accession Numbers: Coordinates for the SrtBΔN30-MTSET, SrtBΔN30-E64, and SrtBΔN30-MTSET-(Gly)3 have been deposited in the Protein Data Bank, with accession codes 1QWZ, 1QX6, and 1QXA respectively.Additional details
- Eprint ID
- 101802
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- CaltechAUTHORS:20200309-161405513
- NASA
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2020-03-10Created from EPrint's datestamp field
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2021-11-16Created from EPrint's last_modified field