1pj3
From Proteopedia
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Crystal structure of human mitochondrial NAD(P)+-dependent malic enzyme in a pentary complex with natural substrate pyruvate, cofactor NAD+, Mn++, and allosteric activator fumarate.
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Overview
Malic enzymes catalyze the oxidative decarboxylation of L-malate to, pyruvate and CO(2) with the reduction of the NAD(P)(+) cofactor in the, presence of divalent cations. We report the crystal structures at up to, 2.1 A resolution of human mitochondrial NAD(P)(+)-dependent malic enzyme, in different pentary complexes with the natural substrate malate or, pyruvate, the dinucleotide cofactor NAD(+) or NADH, the divalent cation, Mn(2+), and the allosteric activator fumarate. Malate is bound deep in the, active site, providing two ligands for the cation, and its C4 carboxylate, group is out of plane with the C1-C2-C3 atoms, facilitating, decarboxylation. The divalent cation is positioned optimally to catalyze, the entire reaction. Lys183 is the general base for the oxidation step, extracting the proton from the C2 hydroxyl of malate. Tyr112-Lys183, functions as the general acid-base pair to catalyze the tautomerization of, the enolpyruvate product from decarboxylation to pyruvate.
Disease
Known disease associated with this structure: Epilepsy, idopathic generalized, susceptibility to OMIM:[154270]
About this Structure
1PJ3 is a Single protein structure of sequence from Homo sapiens with MN, PYR, NAD and FUM as ligands. Active as Malate dehydrogenase (decarboxylating), with EC number 1.1.1.39 Full crystallographic information is available from OCA.
Reference
Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism., Tao X, Yang Z, Tong L, Structure. 2003 Sep;11(9):1141-50. PMID:12962632
Page seeded by OCA on Mon Nov 12 18:43:37 2007
