1pjl

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1pjl, resolution 2.9Å

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Crystal structure of human m-NAD-ME in ternary complex with NAD and Lu3+

Contents

Overview

The catalytic activity of malic enzyme (ME), a member of a new class of, oxidative decarboxylases, requires the presence of divalent cations, (Mn(2+), Mg(2+), and others). The crystal structure at 2.9 A resolution of, human mitochondrial NAD(+)-dependent malic enzyme in a ternary complex, with NAD(+) and the lanthanide ion Lu(3+), which has similar radius as, Mn(2+), reveals a new conformation of the enzyme. The active site in this, ternary complex is in an open form, while the organization of the tetramer, of the enzyme actually resembles that with a closed active site. The, Lu(3+) ion is bound to the enzyme at the same site as Mn(2+). Kinetic, studies showed that Lu(3+) is a potent inhibitor of both the human, NAD(P)(+)-dependent ME and the NADP(+)-dependent ME from pigeon liver, and, is competitive with respect to the divalent cation, consistent with the, structural information.

Disease

Known disease associated with this structure: Epilepsy, idopathic generalized, susceptibility to OMIM:[154270]

About this Structure

1PJL is a Single protein structure of sequence from Homo sapiens with LU and NAD as ligands. Active as Malate dehydrogenase (oxaloacetate-decarboxylating), with EC number 1.1.1.38 Full crystallographic information is available from OCA.

Reference

Potent and competitive inhibition of malic enzymes by lanthanide ions., Yang Z, Batra R, Floyd DL, Hung HC, Chang GG, Tong L, Biochem Biophys Res Commun. 2000 Aug 2;274(2):440-4. PMID:10913357

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