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 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 (decarboxylating), with EC number 1.1.1.44 Resources: FirstGlance, OCA, RCSB, PDBsum 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

Proteopedia Page Contributors and Editors (what is this?)

OCA