3atr
Geranylgeranyl Reductase (GGR) from Sulfolobus acidocaldarius co-crystallized with its ligandGeranylgeranyl Reductase (GGR) from Sulfolobus acidocaldarius co-crystallized with its ligand
Structural highlights
FunctionGGR_SULAC Is involved in the reduction of 2,3-digeranylgeranylglycerophospholipids (unsaturated archaeols) into 2,3-diphytanylglycerophospholipids (saturated archaeols) in the biosynthesis of archaeal membrane lipids. Catalyzes the formation of archaetidic acid (2,3-di-O-phytanyl-sn-glyceryl phosphate) from 2,3-di-O-geranylgeranylglyceryl phosphate (DGGGP) via the hydrogenation of each double bond of the isoprenoid chains. Is not active with NADPH or NADH as an electron donor; the physiological reducing agent is unknown. Is also active on the more upstream precursors of membrane lipid biosynthesis, catalyzing the complete reduction of 3-O-geranylgeranylglyceryl phosphate (GGGP) to 3-O-phytanylglyceryl phosphate, and the partial reduction of geranylgeranyl diphosphate (GGPP) to phytyl diphosphate, thus reducing three of four GGPP double bonds and preserving the allylic double bond (at position 2). This reaction product is a reactive prenyl donor, which can be used as a substrate by archaeal prenyltransferases such as GGGP synthases.[1] [2] [3] Publication Abstract from PubMedThe crystal structure of geranylgeranyl reductase (GGR) from Sulfolobus acidocaldarius was determined in order to elucidate the molecular mechanism of the catalytic reaction. The enzyme is a flavoprotein and is involved in saturation of the double bonds on the isoprenoid moiety of archaeal membranes. The structure determined in this study belongs to the p-hydroxybenzoate hydroxylase family in the glutathione reductase superfamily. GGR functions as a monomer and is divided into the FAD-binding, catalytic and C-terminal domains. The catalytic domain has a large cavity surrounded by a characteristic YxWxFPx(7-8)GxG motif and by the isoalloxazine ring of an FAD molecule. The cavity holds a lipid molecule, which is probably derived from Escherichia coli cells used for over-expression. One of the two forms of the structure clarifies the presence of an anion pocket holding a pyrophosphate molecule, which might anchor the phosphate head of the natural ligands. Mutational analysis supports the suggestion that the three aromatic residues of the YxWxFPx(7-8)GxG motif hold the ligand in the appropriate position for reduction. Cys47, which is widely conserved in GGRs, is located at the si-side of the isoalloxazine ring of FAD and is shown by mutational analysis to be involved in catalysis. The catalytic cycle, including the FAD reducing factor binding site, is proposed on the basis of the detailed analysis of the structure. Structure and mutation analysis of archaeal geranylgeranyl reductase.,Sasaki D, Fujihashi M, Iwata Y, Murakami M, Yoshimura T, Hemmi H, Miki K J Mol Biol. 2011 Jun 17;409(4):543-57. Epub 2011 Apr 16. PMID:21515284[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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