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Anchoring of Surface Proteins to the Cell Wall of Staphylococcus aureus: cysteine 184 and histidine 120 of sortase form a thiolate-imidazolium ion pair for catalysis

Ton-That, Hung and Mazmanian, Sarkis K. and Alksne, Lefa and Schneewind, Olaf (2002) Anchoring of Surface Proteins to the Cell Wall of Staphylococcus aureus: cysteine 184 and histidine 120 of sortase form a thiolate-imidazolium ion pair for catalysis. Journal of Biological Chemistry, 277 (9). pp. 7447-7452. ISSN 0021-9258. https://resolver.caltech.edu/CaltechAUTHORS:TONjbc02

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Abstract

Surface proteins of Staphylococcus aureus are anchored to the cell wall peptidoglycan by a mechanism requiring a C-terminal sorting signal with a LPXTG motif. Sortase cleaves polypeptides between the threonine and the glycine of the LPXTG motif. The carboxyl group of threonine is subsequently amide-linked to the amino group of peptidoglycan cross-bridges. The three-dimensional structure of sortase revealed the close proximity of the catalytic site residue cysteine 184 with histidine 120; however, no structural evidence for a thiolate-imidazolium ion pair could be detected. We report that alanine substitution of either cysteine 184 or histidine 120 abolishes in vivo and in vitro sorting reactions. Further, alanine substitution of tryptophan 194, a residue that is in close proximity of histidine 120, reduces the transpeptidase activity of sortase. These results suggest a model whereby sortase forms a thiolate-imidazolium ion pair for the catalysis of its transpeptidation reaction and that the position of tryptophan 194 assists in the formation of this ion pair.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1074/jbc.M109945200DOIArticle
ORCID:
AuthorORCID
Mazmanian, Sarkis K.0000-0003-2713-1513
Additional Information:© 2002 by The American Society for Biochemistry and Molecular Biology, Inc. Received for publication, October 15, 2001, and in revised form, November 16, 2001. Originally published In Press as doi:10.1074/jbc.M109945200 on November 19, 2001 We thank Pamela Burgio (Wyeth-Ayerst Research) for a-LPETG-d peptide, Steven J. Projan (Wyeth-Ayerst Research), and Dominique M. Missiakas (University of Chicago) for discussion, and members of our laboratory for critical reading of this manuscript. This work was supported in part by United States Public Health Service Grant AI38897. This is paper II in the series Anchoring of Surface Proteins to the Cell Wall of Staphylococcus aureus.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. [H.T.-T. was] Supported in part by the Postdoctoral Training Program in Microbial Pathogenesis at UCLA Grant AI07323. [S.K.M. was] Supported by a Dissertation Year Fellowship from UCLA. [O.S.'s] Laboratory supported by a Grant AI33987 from NIAID, National Institutes of Health.
Funders:
Funding AgencyGrant Number
NIHAI38897
NIH Postdoctoral FellowshipAI07323
UCLAUNSPECIFIED
Issue or Number:9
Record Number:CaltechAUTHORS:TONjbc02
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:TONjbc02
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:6041
Collection:CaltechAUTHORS
Deposited By: Archive Administrator
Deposited On:15 Nov 2006
Last Modified:16 Apr 2020 20:59

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