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Titolo:
Kinetic competence of the cADP-ribose-CD38 complex as an intermediate in the CD38/NAD(+) glycohydrolase-catalysed reactions: implication for CD38 signalling
Autore:
Cakir-Kiefer, I; Muller-Steffner, H; Oppenheimer, N; Schuber, F;
Indirizzi:
Fac Pharm, Chim Bioorgan Lab, ULP, CNRS,UMR 7514, F-67400 Strasbourg, France Fac Pharm Strasbourg France F-67400 UMR 7514, F-67400 Strasbourg, France Univ Calif San Francisco, Sch Pharm, Dept Pharmaceut Chem, San Francisco, CA 94130 USA Univ Calif San Francisco San Francisco CA USA 94130 ancisco, CA 94130 USA
Titolo Testata:
BIOCHEMICAL JOURNAL
, volume: 358, anno: 2001,
parte:, 2
pagine: 399 - 406
SICI:
0264-6021(20010901)358:<399:KCOTCC>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYCLIC ADP-RIBOSE; T-LYMPHOCYTES; ENZYME; MECHANISM; CYCLASE; PURIFICATION; LOCALIZATION; HYDROLYSIS; NAD(+); CYCLIZATION;
Keywords:
cADP-ribose analogues; ectoenzymes; kinetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Schuber, F Fac Pharm, Chim Bioorgan Lab, ULP, CNRS,UMR 7514, 74 Route Rhin, F-67400 Strasbourg, France Fac Pharm 74 Route Rhin Strasbourg France F-67400 ourg, France
Citazione:
I. Cakir-Kiefer et al., "Kinetic competence of the cADP-ribose-CD38 complex as an intermediate in the CD38/NAD(+) glycohydrolase-catalysed reactions: implication for CD38 signalling", BIOCHEM J, 358, 2001, pp. 399-406

Abstract

CD38/NAD(+) glycohydrolase is a type II transmembrane glycoprotein widely used to study T- and B-cell activation and differentiation. CD38 is endowedwith two different activities: it is a signal transduction molecule and anectoenzyme that converts NAD(+) into ADP-ribose (NAD(+) glycohydrolase activity) and small proportions of cADP-ribose (cADPR; ADP-ribosyl cyclase activity), a calcium-mobilizing metabolite, which, ultimately, can also be hydrolysed (cADPR hydrolase activity). The relationship between these two properties, and strikingly the requirement for signalling in the formation of free or enzyme-complexed cADPR, is still ill-defined. In the present study we wanted to test whether the CD38-cADPR complex is kinetically competent inthe conversion of NAD(+) into the reaction product ADP-ribose. In principle, such a complex could be invoked for cross-talk, via conformational changes, with neighbouring partner(s) of CD38 thus triggering the signalling phenomena. Analysis of the kinetic parameters measured for the CD38/NAD(+) glycohydrolase-catalysed hydrolysis of 2'-deoxy-2'-aminoribo-NAD(+) and ADP-cyclo[N1,C1']-2'-deoxy-2'-aminoribose (slowly hydrolysable analogues of NAD(+) and cADPR respectively) ruled out that the CD38-cADPR complex can accumulate under steady-state conditions. This was borne out by simulation of the prevalent kinetic mechanism of CD38, which involve the partitioning of a common E . ADP-ribosyl intermediate in the formation of the enzyme-catalysed reaction products. Using this mechanism, microscopic rate conditions were found which transform a NAD(+) glycohydrolase into an ADP-ribosyl cyclase. Altogether, the present work shows that if the cross-talk with a partner depends on a conformational change of CD38, this is most probably not attributable to the formation of the CD38-cADPR complex. In line with recent results on the conformational change triggered by CD38 ligands [Berthelier, Laboureau, Boulla, Schuber and Deterre (2000) Eur. J. Biochem. 267, 3056-3064], we believe that the Michaelis CD38-NAD(+) complex could play such a role instead.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 18:45:34