1djl
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THE CRYSTAL STRUCTURE OF HUMAN TRANSHYDROGENASE DOMAIN III WITH BOUND NADP
OverviewOverview
BACKGROUND: Transhydrogenase, located in the inner membranes of animal, mitochondria and the cytoplasmic membranes of bacteria, couples the, transfer of reducing equivalents between NAD(H) and NADP(H) to proton, pumping. The protein comprises three subunits termed dI, dII and dIII. The, dII component spans the membrane. The dI component, which contains the, binding site for NAD(+)/NADH, and the dIII component, which has the, binding site for NADP(+)/NADPH, protrude from the membrane. Proton pumping, is probably coupled to changes in the binding affinities of dIII for, NADP(+) and NADPH. RESULTS: The first X-ray structure of the, NADP(H)-binding component, dIII, of human heart transhydrogenase is, described here at 2.0 A resolution. It comprises a single domain, resembling the classical Rossmann fold, but NADP(+) binds to dIII with a, reversed orientation. The first betaalphabetaalphabeta motif of dIII, contains a Gly-X-Gly-X-X-Ala/Val 'fingerprint', but it has a different, function to that in the classical Rossmann structure. The nicotinamide, ring of NADP(+) is located on a ridge where it is exposed to interaction, with NADH on the dI subunit. Two distinctive features of the dIII, structure are helix D/loop D, which projects from the beta sheet, and loop, E, which forms a 'lid' over the bound NADP(+). CONCLUSIONS: Helix D/loop D, interacts with the bound nucleotide and loop E, and probably interacts, with the membrane-spanning dII. Changes in ionisation and conformation in, helix D/loop D, resulting from proton translocation through dII, are, thought to be responsible for the changes in affinity of dIII for NADP(+), and NADPH that drive the reaction.
About this StructureAbout this Structure
1DJL is a Single protein structure of sequence from Homo sapiens with SO4, NAP and GOL as ligands. Active as NAD(P)(+) transhydrogenase (B-specific), with EC number 1.6.1.1 Full crystallographic information is available from OCA.
ReferenceReference
The high-resolution structure of the NADP(H)-binding component (dIII) of proton-translocating transhydrogenase from human heart mitochondria., White SA, Peake SJ, McSweeney S, Leonard G, Cotton NP, Jackson JB, Structure. 2000 Jan 15;8(1):1-12. PMID:10673423
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