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

J. Biol. Chem., Vol. 281, Issue 14, 9547-9551, April 7, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/14/9547    most recent M510550200v1 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 Bartolommei, G. Articles by Guidelli, R. Search for Related Content PubMed PubMed Citation Articles by Bartolommei, G. Articles by Guidelli, R. Social Bookmarking                      What's this?

Clotrimazole Inhibits the Ca²⁺-ATPase (SERCA) by Interfering with Ca²⁺ Binding and Favoring the E2 Conformation^*

Gianluca Bartolommei, Francesco Tadini-Buoninsegni, Suming Hua, Maria Rosa Moncelli, Giuseppe Inesi, and Rolando Guidelli¹

From the Department of Chemistry, University of Florence, 50019 Sesto Fiorentino, Florence, Italy and the Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201

Clotrimazole (CLT) is an antimycotic imidazole derivative that is known to inhibit cytochrome P-450, ergosterol biosynthesis and proliferation of cells in culture, and to interfere with cellular Ca²⁺ homeostasis. We found that CLT inhibits the Ca²⁺-ATPase of rabbit fast-twitch skeletal muscle (SERCA1), and we characterized in detail the effect of CLT on this calcium transport ATPase. We used biochemical methods for characterization of the ATPase and its partial reactions, and we also performed measurements of charge movements following adsorption of sarcoplasmic reticulum vesicles containing the ATPase onto a gold-supported biomimetic membrane. CLT inhibits Ca²⁺-ATPase and Ca²⁺ transport with a K_I of 35 µM. Ca²⁺ binding in the absence of ATP and phosphoenzyme formation by the utilization of ATP in the presence of Ca²⁺ are also inhibited within the same CLT concentration range. On the other hand, phosphoenzyme formation by utilization of P_i in the absence of Ca²⁺ is only minimally inhibited. It is concluded that CLT inhibits primarily Ca²⁺ binding and, consequently, the Ca²⁺-dependent reactions of the SERCA cycle. It is suggested that CLT resides within the membrane-bound region of the transport ATPase, thereby interfering with binding and the conformational effects of the activating cation.

Received for publication, September 27, 2005 , and in revised form, December 14, 2005.

^* This work was supported by the Ente Cassa di Risparmio di Firenze (PROMELAB project) the Ministero dell'Istruzione, dell'Università e della Ricerca, and National Institutes of Health Grant RO1 HL69830. 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: Dept. of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy. Tel.: 39-055-4573097; Fax: 39-055-4573098; E-mail: guidelli{at}unifi.it.

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

This article has been cited by other articles:

				G. Bartolommei, N. Devaux, F. Tadini-Buoninsegni, M. Moncelli, and H.-J. Apell Effect of Clotrimazole on the Pump Cycle of the Na,K-ATPase Biophys. J., August 15, 2008; 95(4): 1813 - 1825. [Abstract] [Full Text] [PDF]

				Y. A. Mahmmoud Capsaicin Stimulates Uncoupled ATP Hydrolysis by the Sarcoplasmic Reticulum Calcium Pump J. Biol. Chem., August 1, 2008; 283(31): 21418 - 21426. [Abstract] [Full Text] [PDF]

				F. Tadini-Buoninsegni, G. Bartolommei, M. R. Moncelli, R. Guidelli, and G. Inesi Pre-steady State Electrogenic Events of Ca2+/H+ Exchange and Transport by the Ca2+-ATPase J. Biol. Chem., December 8, 2006; 281(49): 37720 - 37727. [Abstract] [Full Text] [PDF]