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Journal of Bacteriology, July 2005, p. 4928-4934, Vol. 187, No. 14
0021-9193/05/$08.00+0     doi:10.1128/JB.187.14.4928-4934.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Genome-Wide Detection and Analysis of Cell Wall-Bound Proteins with LPxTG-Like Sorting Motifs

Centre for Molecular and Biomolecular Informatics, Radboud University Nijmegen, 6525ED Nijmegen, The Netherlands,¹ Wageningen Centre for Food Sciences, Wageningen, The Netherlands,² NIZO Food Research, Ede, The Netherlands³

Received 19 January 2005/ Accepted 17 April 2005

Surface proteins of gram-positive bacteria often play a role in adherence of the bacteria to host tissue and are frequently required for virulence. A specific subgroup of extracellular proteins contains the cell wall-sorting motif LPxTG, which is the target for cleavage and covalent coupling to the peptidoglycan by enzymes called sortases. A comprehensive set of putative sortase substrates was identified by in silico analysis of 199 completely sequenced prokaryote genomes. A combination of detection methods was used, including secondary structure prediction, pattern recognition, sequence homology, and genome context information. With the hframe algorithm, putative substrates were identified that could not be detected by other methods due to errors in open reading frame calling, frameshifts, or sequencing errors. In total, 732 putative sortase substrates encoded in 49 prokaryote genomes were identified. We found striking species-specific variation for the LPxTG motif. A hidden Markov model (HMM) based on putative sortase substrates was created, which was subsequently used for the automatic detection of sortase substrates in recently completed genomes. A database was constructed, LPxTG-DB (http://bamics3.cmbi.kun.nl/sortase_substrates), containing for each genome a list of putative sortase substrates, sequence information of these substrates, the organism-specific HMMs based on the consensus sequence of the sortase recognition motif, and a graphic representation of this consensus.

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