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

J. Biol. Chem., Vol. 281, Issue 3, 1516-1523, January 20, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/3/1516    most recent M506947200v1 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 Espiau, B. Articles by Bakalara, N. Search for Related Content PubMed PubMed Citation Articles by Espiau, B. Articles by Bakalara, N. Social Bookmarking                      What's this?

A Soluble Pyrophosphatase, a Key Enzyme for Polyphosphate Metabolism in Leishmania^*

From the Laboratoire de Génomique Fonctionnelle des Trypanosomatides, Université Victor Segalen Bordeaux 2, UMR-CNRS 5162, 146 rue Léo Saignat, 33076 Bordeaux, France

We report the functional characterization in Leishmania amazonensis of a soluble pyrophosphatase (LaVSP1) that localizes in acidocalcisomes, a vesicular acidic compartment. LaVSP1 is preferentially expressed in metacyclic forms. Experiments with dominant negative mutants show the requirement of LaVSP1 functional expression for metacyclogenesis and virulence in mice. Depending on the pH and the cofactors Mg²⁺ or Zn²⁺, both present in acidocalcisomes, LaVSP1 hydrolyzes either inorganic pyrophosphate (K_m = 92 µM, k_cat = 125 s^–1), tripolyphosphate (K_m = 1153 µM, k_cat = 131 s^–1), or polyphosphate of 28 residues (K_m = 123 µM, k_cat = 8 s^–1). Predicted structural analysis suggests that the structural orientation of the residue Lys⁷⁸ in LaVSP1 accounts for the observed increase in K_m compared with the yeast pyrophosphatase and for the ability of trypanosomatid VSP1 enzymes to hydrolyze polyphosphate. These results make the VSP1 enzyme an attractive drug target against trypanosomatid parasites.

Received for publication, June 27, 2005 , and in revised form, November 15, 2005.

^* This work was supported by the CNRS, the Conseil Régional d'Aquitaine, the GDR CNRS-Parasitologie, and the Ministère de l'Education Nationale de la Recherche et de la Technologie (Action Microbiologie). 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.

¹ To whom correspondence should be addressed: Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale 34296 Montpellier, France. Tel.: 33-467-668-601; Fax: 33-467-548-610; E-mail: norbert.bakalara{at}enscm.fr.

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

This article has been cited by other articles:

				S. Besteiro, D. Tonn, L. Tetley, G. H. Coombs, and J. C. Mottram The AP3 adaptor is involved in the transport of membrane proteins to acidocalcisomes of Leishmania J. Cell Sci., March 1, 2008; 121(5): 561 - 570. [Abstract] [Full Text] [PDF]