1hwy
From Proteopedia
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BOVINE GLUTAMATE DEHYDROGENASE COMPLEXED WITH NAD AND 2-OXOGLUTARATE
Overview
Glutamate dehydrogenase is found in all organisms and catalyses the, oxidative deamination of l-glutamate to 2-oxoglutarate. However, only, animal GDH utilizes both NAD(H) or NADP(H) with comparable efficacy and, exhibits a complex pattern of allosteric inhibition by a wide variety of, small molecules. The major allosteric inhibitors are GTP and NADH and the, two main allosteric activators are ADP and NAD(+). The structures, presented here have refined and modified the previous structural model of, allosteric regulation inferred from the original boGDH.NADH.GLU.GTP, complex. The boGDH.NAD(+).alpha-KG complex structure clearly demonstrates, that the second coenzyme-binding site lies directly under the "pivot, helix" of the NAD(+) binding domain. In this complex, phosphates are, observed to occupy the inhibitory GTP site and may be responsible for the, previously observed structural stabilization by polyanions. The, boGDH.NADPH.GLU.GTP complex shows the location of the additional phosphate, on the active site coenzyme molecule and the GTP molecule bound to the GTP, inhibitory site. As expected, since NADPH does not bind well to the second, coenzyme site, no evidence of a bound molecule is observed at the second, coenzyme site under the pivot helix. Therefore, these results suggest that, the inhibitory GTP site is as previously identified. However, ADP, NAD(+), and NADH all bind under the pivot helix, but a second GTP molecule does, not. Kinetic analysis of a hyperinsulinism/hyperammonemia mutant strongly, suggests that ATP can inhibit the reaction by binding to the GTP site., Finally, the fact that NADH, NAD(+), and ADP all bind to the same site, requires a re-analysis of the previous models for NADH inhibition.
About this Structure
1HWY is a Single protein structure of sequence from Bos taurus with PO4, AKG and NAD as ligands. Active as Glutamate dehydrogenase (NAD(P)(+)), with EC number 1.4.1.3 Full crystallographic information is available from OCA.
Reference
Structures of bovine glutamate dehydrogenase complexes elucidate the mechanism of purine regulation., Smith TJ, Peterson PE, Schmidt T, Fang J, Stanley CA, J Mol Biol. 2001 Mar 23;307(2):707-20. PMID:11254391
Page seeded by OCA on Tue Nov 20 16:52:18 2007
