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

J. Biol. Chem., Vol. 282, Issue 34, 24990-24999, August 24, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/34/24990    most recent M704317200v1 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 Pérez-Dorado, I. Articles by Hermoso, J. A. Search for Related Content PubMed PubMed Citation Articles by Pérez-Dorado, I. Articles by Hermoso, J. A. Social Bookmarking                      What's this?

Elucidation of the Molecular Recognition of Bacterial Cell Wall by Modular Pneumococcal Phage Endolysin CPL-1^*

Inmaculada Pérez-Dorado¹, Nuria E. Campillo, Begoña Monterroso^¶, Dusan Hesek^||, Mijoon Lee^||, Juan A. Páez, Pedro García^**, Martín Martínez-Ripoll, José L. García^**, Shahriar Mobashery^||, Margarita Menéndez^¶, and Juan A. Hermoso²

From the Grupo de Cristalografía Macromolecular y Biología Estructural, Instituto de Química-Física Rocasolano, CSIC, Serrano 119, 28006 Madrid, Spain, the Departamento de Quimioterapia, Instituto de Química Médica, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain, the ^¶Departamento de Química-Física de Macromoléculas Biológicas, Instituto Química-Física Rocasolano, CSIC, Serrano 119, 28006 Madrid, Spain, the ^||Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, and the ^**Departamento de Microbiología Molecular, Centro de Investigaciones Biológicas, CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain

Pneumococcal bacteriophage-encoded lysins are modular proteins that have been shown to act as enzymatic antimicrobial agents (enzybiotics) in treatment of streptococcal infections. The first x-ray crystal structures of the Cpl-1 lysin, encoded by the pneumococcal phage Cp-1, in complex with three bacterial cell wall peptidoglycan (PG) analogues are reported herein. The Cpl-1 structure is folded in two well defined modules, one responsible for anchoring to the pneumococcal cell wall and the other, a catalytic module, that hydrolyzes the PG. Conformational rearrangement of Tyr-127 is a critical event in molecular recognition of a stretch of five saccharide rings of the polymeric peptidoglycan (cell wall). The PG is bound at a stretch of the surface that is defined as the peptidoglycan-binding sites 1 and 2, the juncture of which catalysis takes place. The peptidoglycan-binding site 1 binds to a stretch of three saccharides of the peptidoglycan in a conformation essentially identical to that of the peptidoglycan in solution. In contrast, binding of two peptidoglycan saccharides at the peptidoglycan-binding site 2 introduces a kink into the solution structure of the peptidoglycan, en route to catalytic turnover. These findings provide the first structural evidence on recognition of the peptidoglycan and shed light on the discrete events of cell wall degradation by Cpl-1.

Received for publication, May 25, 2007 , and in revised form, June 12, 2007.

The atomic coordinates and structure factors (code 2ixu, 2ixv, 2j8f, and 2j8g) 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 by Grants BFU2005-01645, BIO2003-01952, and BFU2006-10288 from Dirección General de Investigación by 08.2/0030.1/2003 from the Comunidad de Madrid, by "Factoria de Cristalización," CONSOLIDER INGENIO-2010, and by a grant from the National Institutes of Health. 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 Tables 2 and 3 and Figs. 1 and 2.

¹ Previously a fellow of the Consejo Superior de Investigaciones Científicas.

² To whom correspondence should be addressed. Tel.: 34-915619400; Fax: 34-915642431; E-mail: xjuan{at}iqfr.csic.es.

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

This article has been cited by other articles:

				B. Monterroso, J. L. Saiz, P. Garcia, J. L. Garcia, and M. Menendez Insights into the Structure-Function Relationships of Pneumococcal Cell Wall Lysozymes, LytC and Cpl-1 J. Biol. Chem., October 17, 2008; 283(42): 28618 - 28628. [Abstract] [Full Text] [PDF]