http://www.cnr.it/ontology/cnr/individuo/prodotto/ID9936

FAD-Binding Site and NADP Reactivity in Human Renalase: A New Enzyme Involved in Blood Pressure Regulation (Articolo in rivista)

Type

Articolo in rivista (Classe)
Prodotto della ricerca (Classe)

Label

FAD-Binding Site and NADP Reactivity in Human Renalase: A New Enzyme Involved in Blood Pressure Regulation (Articolo in rivista) (literal)

Anno

2011-01-01T00:00:00+01:00 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

10.1016/j.jmb.2011.06.010 (literal)

Alternative label

Milani, Mario; Ciriello, Francesco; Baroni, Sara; Pandini, Vittorio; Canevari, Giulia; Bolognesi, Martino; Aliverti, Alessandro (2011)
FAD-Binding Site and NADP Reactivity in Human Renalase: A New Enzyme Involved in Blood Pressure Regulation
in Journal of Molecular Biology
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Milani, Mario; Ciriello, Francesco; Baroni, Sara; Pandini, Vittorio; Canevari, Giulia; Bolognesi, Martino; Aliverti, Alessandro (literal)

Pagina inizio

463 (literal)

Pagina fine

473 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

411 (literal)

Rivista

Journal of Molecular Biology (Rivista)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#pagineTotali

11 (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

2 (literal)

Note

ISI Web of Science (WOS) (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

University of Milan; University of Milan; Nerviano Med Sci (literal)

Titolo

FAD-Binding Site and NADP Reactivity in Human Renalase: A New Enzyme Involved in Blood Pressure Regulation (literal)

Abstract

Renalase is a recently discovered flavoprotein that regulates blood pressure, regulates sodium and phosphate excretion, and displays cardioprotectant action through a mechanism that is barely understood to date. It has been proposed to act as a catecholamine-degrading enzyme, via either O(2)-dependent or NADH-dependent mechanisms. Here we report the renalase crystal structure at 2.5 angstrom resolution together with new data on its interaction with nicotinamide dinucleotides. Renalase adopts the p-hydroxybenzoate hydroxylase fold topology, comprising a Rossmann-fold-based flavin adenine dinucleotide (FAD)-binding domain and a putative substrate-binding domain, the latter of which contains a five-stranded anti-parallel beta-sheet. A large cavity (228 angstrom(3)), facing the flavin ring, presumably represents the active site. Compared to monoamine oxidase or polyamine oxidase, the renalase active site is fully solvent exposed and lacks an 'aromatic cage' for binding the substrate amino group. Renalase has an extremely low diaphorase activity, displaying lower k(cat) but higher k(cat)/K(m) for NADH compared to NADPH. Moreover, its FAD prosthetic group becomes slowly reduced when it is incubated with NADPH under anaerobiosis, and binds NAD(+) or NADP(+) with K(d) values of ca 2 mM. The absence of a recognizable NADP-binding site in the protein structure and its poor affinity for, and poor reactivity towards, NADH and NADPH suggest that these are not physiological ligands of renalase. Although our study does not answer the question on the catalytic activity of renalase, it provides a firm framework for testing hypotheses on the molecular mechanism of its action. (C) 2011 Elsevier Ltd. All rights reserved. (literal)

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