1ptj
Crystal structure analysis of the DI and DIII complex of transhydrogenase with a thio-nicotinamide nucleotide analogue
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OverviewOverview
Transhydrogenase couples the reduction of NADP+ by NADH to inward proton, translocation across mitochondrial and bacterial membranes. The coupling, reactions occur within the protein by long distance conformational, changes. In intact transhydrogenase and in complexes formed from the, isolated, nucleotide-binding components, thio-NADP(H) is a good analogue, for NADP(H), but thio-NAD(H) is a poor analogue for NAD(H). Crystal, structures of the nucleotide-binding components show that the twists of, the 3-carbothiamide groups of thio-NADP+ and of thio-NAD+ (relative to the, planes of the pyridine rings), which are defined by the dihedral, Xam, are, altered relative to the twists of the 3-carboxamide groups of the, physiological nucleotides. The finding that thio-NADP+ is a good substrate, despite an increased Xam value shows that approach of the NADH prior to, hydride transfer is not obstructed by the S atom in the analogue. That, thio-NAD(H) is a poor substrate appears to be the result of failure in the, conformational change that establishes the ground state for hydride, transfer. This might be a consequence of restricted rotation of the, 3-carbothiamide group during the conformational change.
About this StructureAbout this Structure
1PTJ is a Protein complex structure of sequences from Rhodospirillum rubrum with SND, NAP and GOL as ligands. Active as NAD(P)(+) transhydrogenase (AB-specific), with EC number 1.6.1.2 Full crystallographic information is available from OCA.
ReferenceReference
Interactions between transhydrogenase and thio-nicotinamide Analogues of NAD(H) and NADP(H) underline the importance of nucleotide conformational changes in coupling to proton translocation., Singh A, Venning JD, Quirk PG, van Boxel GI, Rodrigues DJ, White SA, Jackson JB, J Biol Chem. 2003 Aug 29;278(35):33208-16. Epub 2003 Jun 5. PMID:12791694
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