TAILIEUCHUNG - Báo cáo khoa học: Enzymatic oxidation of NADP+ to its 4-oxo derivative is a side-reaction displayed only by the adrenodoxin reductase type of ferredoxin-NADP+ reductases

We have previously shown thatMycobacterium tuberculosisFprA, an NADPH-ferredoxin reductase homologous to mammalian adrenodoxin reductase, promotes the oxidation of NADP + to its 4-oxo derivative 3-car-boxamide-4-pyridone adenine dinucleotide phosphate [Bossi RT, Aliverti A, Raimondi D, Fischer F, Zanetti G, Ferrari D, Tahallah N, Maier CS, Heck AJ, Rizzi Met al. | ễFEBS Journal Enzymatic oxidation of NADP to its 4-oxo derivative is a side-reaction displayed only by the adrenodoxin reductase type of ferredoxin-NADP reductases Matteo de Rosa1 Andrea Pennati1 Vittorio Pandini1 Enrico Monzani2 Giuliana Zanetti1 and Alessandro Aliverti1 1 Dipartimento di Scienze Biomolecolari e Biotecnologie University degli Studi di Milano Italy 2 Dipartimento di Chimica Generale University degli Studi di Pavia Italy Keywords adrenodoxin reductase 3-carboxamide-4-pyridone adenine dinucleotide phosphate flavoprotein Mycobacterium tuberculosis NADP derivative Correspondence A. Aliverti Dipartimento di Scienze Biomolecolari e Biotecnologie via Celoria 26 20133 Milano Italy Fax 39 02 50314895 Tel 39 02 50314897 E-mail Website http Received 19 March 2007 revised 7 May 2007 accepted 11 June 2007 doi We have previously shown that Mycobacterium tuberculosis FprA an NADPH-ferredoxin reductase homologous to mammalian adrenodoxin reductase promotes the oxidation of NADP to its 4-oxo derivative 3-car-boxamide-4-pyridone adenine dinucleotide phosphate Bossi RT Aliverti A Raimondi D Fischer F Zanetti G Ferrari D Tahallah N Maier CS Heck AJ Rizzi M et al. 2002 Biochemistry 41 8807-8818 . Here we provide a detailed study of this unusual enzyme reaction showing that it occurs at a very slow rate h 1 requires the participation of the enzyme-bound FAD and is regiospecific in affecting only the C4 of the NADP nicotinamide ring. By protein engineering we excluded the involvement in catalysis of residues Glu214 and His57 previously suggested to be implicated on the basis of their localization in the three-dimensional structure of the enzyme. Our results substantiate a catalytic mechanism for 3-carboxamide-4-pyridone adenine dinucleotide phosphate formation in which the initial and rate-determining step is the nucleophilic attack of the nicotinamide moiety by an active site .

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