1pgp

CRYSTALLOGRAPHIC STUDY OF COENZYME, COENZYME ANALOGUE AND SUBSTRATE BINDING IN 6-PHOSPHOGLUCONATE DEHYDROGENASE: IMPLICATIONS FOR NADP SPECIFICITY AND THE ENZYME MECHANISM

spinqualitylabelsall models 1pgp, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1pgp is a 1 chain structure with sequence from Ovis ammon aries. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 6PG, SO4 Related: 2pgd, 1pgn, 1pgo, 1pgq Activity: Phosphogluconate dehydrogenase (NADP(+)-dependent, decarboxylating), with EC number 1.1.1.44 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [6PGD_SHEEP] Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed BACKGROUND: The nicotinamide adenine dinucleotide phosphate (NADP)-dependent oxidative decarboxylase, 6-phosphogluconate dehydrogenase, is a major source of reduced coenzyme for synthesis. Enzymes later in the pentose phosphate pathway convert the reaction product, ribulose 5-phosphate, to ribose 5-phosphate. Crystallographic study of complexes with coenzyme and substrate explain the NADP dependence which determines the enzyme's metabolic role and support the proposed general base-general acid mechanism. RESULTS: The refined structures of binary coenzyme/analogue complexes show that Arg33 is ordered by binding the 2'-phosphate, and provides one face of the adenine site. The nicotinamide, while less tightly bound, is more extended when reduced than when oxidized. All substrate binding residues are conserved; the 3-hydroxyl of 6-phosphogluconate is hydrogen bonded to N zeta of Lys183 and the 3-hydrogen points towards the oxidized nicotinamide. The 6-phosphate replaces a tightly bound sulphate in the apo-enzyme. CONCLUSIONS: NADP specificity is achieved primarily by Arg33 which binds the 2'-phosphate but, in its absence, obscures the adenine pocket. The bound oxidized nicotinamide is syn; hydride transfer from bound substrate to the nicotinamide si- face is achieved with a small movement of the nicotinamide nucleotide. Lys183 may act as general base. A water bound to Gly130 in the coenzyme domain is the most likely acid required in decarboxylation. The dihydronicotinamide ring of NADPH competes for ligands with the 1-carboxyl of 6-phosphogluconate. Crystallographic study of coenzyme, coenzyme analogue and substrate binding in 6-phosphogluconate dehydrogenase: implications for NADP specificity and the enzyme mechanism.,Adams MJ, Ellis GH, Gover S, Naylor CE, Phillips C Structure. 1994 Jul 15;2(7):651-68. PMID:7922042 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also 6-phosphogluconate dehydrogenase 3D structures

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