HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 49, 40802-40812, December 9, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/49/40802    most recent M506328200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Korza, H. J. Articles by Bochtler, M. Search for Related Content PubMed PubMed Citation Articles by Korza, H. J. Articles by Bochtler, M. Social Bookmarking                      What's this?

Pseudomonas aeruginosa LD-Carboxypeptidase, a Serine Peptidase with a Ser-His-Glu Triad and a Nucleophilic Elbow^*

From the International Institute of Molecular and Cell Biology, Ulica Trojdena 4, 02-109 Warsaw, Poland and the Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01309 Dresden, Germany

LD-Carboxypeptidases (EC 3.4.17.13 [EC] ) are named for their ability to cleave amide bonds between L- and D-amino acids, which occur naturally in bacterial peptidoglycan. They are specific for the link between meso-diaminopimelic acid and D-alanine and therefore degrade GlcNAc-MurNAc tetrapeptides to the corresponding tripeptides. As only the tripeptides can be reused as peptidoglycan building blocks, LD-carboxypeptidases are thought to play a role in peptidoglycan recycling. Despite the pharmaceutical interest in peptidoglycan biosynthesis, the fold and catalytic type of LD-carboxypeptidases are unknown. Here, we show that a previously uncharacterized open reading frame in Pseudomonas aeruginosa has LD-carboxypeptidase activity and present the crystal structure of this enzyme. The structure shows that the enzyme consists of an N-terminal -sheet and a C-terminal -barrel domain. At the interface of the two domains, Ser¹¹⁵ adopts a highly strained conformation in the context of a strand-turn-helix motif that is similar to the "nucleophilic elbow" in -hydrolases. Ser¹¹⁵ is hydrogen-bonded to a histidine residue, which is oriented by a glutamate residue. All three residues, which occur in the order Ser-Glu-His in the amino acid sequence, are strictly conserved in naturally occurring LD-carboxypeptidases and cannot be mutated to alanines without loss of activity. We conclude that LD-carboxypeptidases are serine peptidases with Ser-His-Glu catalytic triads.

Received for publication, June 10, 2005 , and in revised form, September 9, 2005.

The atomic coordinates and structure factors (code 1ZRS, 2AUM, and 2AUN) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

^* This work was supported in part by Polish Ministry of Scientific Research and Information Technology, Decisions 1789/E-529/SPB/5.PR UE/DZ 600/2002-2005, 158/E-338/SPB/5.PR UE/DZ 19/2003, and KO89/PO4/2004 and by Deutsche Forschungsgemeinschaft Grant BO1733/1-1 (Proteolyse in Prokaryonten: Kontrolle und Regulatorisches Prinzip). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Fig. S1.

¹ Supported by a Young Investigator award from the European Molecular Biology Organization and the Howard Hughes Medical Institute. To whom correspondence should be addressed: International Institute of Molecular and Cell Biology, ul. Trojdena 4, 02-109 Warsaw, Poland. Tel.: 48-22-597-0732; Fax: 48-22-597-0715; E-mail: MBochtler{at}iimcb.gov.pl.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. T. Park and T. Uehara How Bacteria Consume Their Own Exoskeletons (Turnover and Recycling of Cell Wall Peptidoglycan) Microbiol. Mol. Biol. Rev., June 1, 2008; 72(2): 211 - 227. [Abstract] [Full Text] [PDF]

				S. Magnet, A. Arbeloa, J.-L. Mainardi, J.-E. Hugonnet, M. Fourgeaud, L. Dubost, A. Marie, V. Delfosse, C. Mayer, L. B. Rice, et al. Specificity of L,D-Transpeptidases from Gram-positive Bacteria Producing Different Peptidoglycan Chemotypes J. Biol. Chem., May 4, 2007; 282(18): 13151 - 13159. [Abstract] [Full Text] [PDF]

				P. Courtin, G. Miranda, A. Guillot, F. Wessner, C. Mezange, E. Domakova, S. Kulakauskas, and M.-P. Chapot-Chartier Peptidoglycan Structure Analysis of Lactococcus lactis Reveals the Presence of an L,D-Carboxypeptidase Involved in Peptidoglycan Maturation. J. Bacteriol., July 1, 2006; 188(14): 5293 - 5298. [Abstract] [Full Text] [PDF]