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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
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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
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- 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