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The enzyme a-amino-b-carboxymuconate-e-semialdehyde decarboxylase (ACMSD) is a zinc-dependent amidohydrolase that participates in picolinic acid (PA), quinolinic acid (QA) and NAD homeostasis. Indeed, the enzyme stands at a branch point of the tryptophan to NAD pathway, and deter-mines the final fate of the amino acid, i.e. transformation into PA, com-plete oxidation through the citric acid cycle, or conversion into NAD through QA synthesis. | The crystal structure of human a-amino-p-carboxymuconate-e-semialdehyde decarboxylase in complex with 1 3-dihydroxyacetonephosphate suggests a regulatory link between NAD synthesis and glycolysis Silvia Garavaglia1 Silvia Perozzi1 Luca Galeazzi2 Nadia Raffaelli2 and Menico Rizzi1 1 DiSCAFF Dipartimento di Scienze Chimiche Alimentari Farmaceutiche e Farmacologiche University of Piemonte Orientale A. Avogadro Novara Italy 2 Department of Molecular Pathology and Innovative Therapies Section of Biochemistry Universita Politecnica delle Marche Ancona Italy Keywords cerebral malaria kynurenine pathway metal-dependent amidohydrolase NAD biosynthesis neurological disorders Correspondence M. Rizzi DiSCAFF University of Piemonte Orientale Via Bovio 6 28100 Novara Italy Fax 39 0321 375821 Tel 39 0321 375712 E-mail rizzi@pharm.unipmn.it Database The atomic coordinates and structure factors of hACMSD have been deposited with the Protein Data Bank http www.rcsb.org with accession codes 2wm1 and r2wm1 respectively Received 1 July 2009 revised 8 September 2009 accepted 10 September 2009 doi 10.1111 j.1742-4658.2009.07372.x The enzyme a-amino-p-carboxymuconate-e-semialdehyde decarboxylase ACMSD is a zinc-dependent amidohydrolase that participates in picolinic acid PA quinolinic acid QA and NAD homeostasis. Indeed the enzyme stands at a branch point of the tryptophan to NAD pathway and determines the final fate of the amino acid i.e. transformation into PA complete oxidation through the citric acid cycle or conversion into NAD through QA synthesis. Both PA and QA are key players in a number of physiological and pathological conditions mainly affecting the central nervous system. As their relative concentrations must be tightly controlled modulation of ACMSD activity appears to be a promising prospect for the treatment of neurological disorders including cerebral malaria. Here we report the 2.0 A resolution crystal structure of human ACMSD in complex with the glycolytic intermediate
