title: Structural studies suggest a peptidoglycan hydrolase function for the Mycobacterium tuberculosis Tat-secreted protein Rv2525c.
abstract: Among the few proteins shown to be secreted by the Tat system in Mycobacterium tuberculosis, Rv2525c is of particular interest, since its gene is conserved in the minimal genome of Mycobacterium leprae. Previous evidence linked this protein to cell wall metabolism and sensitivity to β-lactams. We describe here the crystal structure of Rv2525c that shows a TIM barrel-like fold characteristic of glycoside hydrolases of the GH25 family, which includes prokaryotic and phage-encoded peptidoglycan hydrolases. Structural comparison with other members of this family combined with substrate docking suggest that, although the 'neighbouring group' catalytic mechanism proposed for this family still appears as the most plausible, the identity of residues involved in catalysis in GH25 hydrolases might need to be revised.
authors.affiliation: Institut Pasteur, Unité de Microbiologie Structurale and CNRS-UMR3528, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France. Electronic address: marco.bellinzoni@pasteur.fr.
authors.forename: Marco
authors.initials: M
authors.lastname: Bellinzoni
authors.affiliation: Institut Pasteur, Plateforme de Cristallographie (CNRS-UMR3528), 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Haouz
authors.affiliation: Institut Pasteur, Plateforme de Cristallographie (CNRS-UMR3528), 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Miras
authors.affiliation: Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Magnet
authors.affiliation: Institut Pasteur, Unité de Microbiologie Structurale and CNRS-UMR3528, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France; Unité Mathématique, Informatique et Génome (MIG), INRA, Domaine de Vilvert, 78352 Jouy en Josas Cedex, France.
authors.forename: Gwénaëlle
authors.initials: G
authors.lastname: André-Leroux
authors.affiliation: Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland.
authors.forename: Raju
authors.initials: R
authors.lastname: Mukherjee
authors.affiliation: Synchrotron Soleil, L'Orme des Merisiers, Saint-Aubin, 91192 Gif-sur-Yvette Cedex, France.
authors.forename: William
authors.initials: W
authors.lastname: Shepard
authors.affiliation: Global Health Institute, Ecole Polytechnique Fédérale de Lausanne, Station 19, 1015 Lausanne, Switzerland.
authors.forename: Stewart T
authors.initials: ST
authors.lastname: Cole
authors.affiliation: Institut Pasteur, Unité de Microbiologie Structurale and CNRS-UMR3528, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Alzari
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000378:metabolism*; D002384:Catalysis; D020134:Catalytic Domain; D002473:Cell Wall / Q000378:metabolism; D018360:Crystallography, X-Ray / Q000379:methods; D015696:Gene Products, tat / Q000378:metabolism*; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D015696:Gene Products, tat; D009238:N-Acetylmuramoyl-L-alanine Amidase
keywords: GH25; Peptidoglycan hydrolase; Tat secretion pathway; Tuberculosis