Structural highlights
FunctionG1PDH_METJA Catalyzes the NAD(P)H-dependent reduction of dihydroxyacetonephosphate (DHAP or glycerone phosphate) to glycerol 1-phosphate (G1P). The G1P thus generated is used as the glycerophosphate backbone of phospholipids in the cellular membranes of Archaea. Publication Abstract from PubMedOne of the most critical events in the origins of cellular life was the development of lipid membranes. Archaea use isoprenoid chains linked via ether bonds to sn-glycerol 1-phosphate (G1P), whereas bacteria and eukaryotes use fatty acids attached via ester bonds to enantiomeric sn-glycerol 3-phosphate. NAD(P)H-dependent G1P dehydrogenase (G1PDH) forms G1P and has been proposed to have played a crucial role in the speciation of the Archaea. We present here, to our knowledge, the first structures of archaeal G1PDH from the hyperthermophilic methanogen Methanocaldococcus jannaschii with bound substrate dihydroxyacetone phosphate, product G1P, NADPH, and Zn(2+) cofactor. We also biochemically characterized the enzyme with respect to pH optimum, cation specificity, and kinetic parameters for dihydroxyacetone phosphate and NAD(P)H. The structures provide key evidence for the reaction mechanism in the stereospecific addition for the NAD(P)H-based pro-R hydrogen transfer and the coordination of the Zn(2+) cofactor during catalysis. Structure-based phylogenetic analyses also provide insight into the origins of G1PDH. Structure and Evolution of the Archaeal Lipid Synthesis Enzyme sn-Glycerol-1-phosphate Dehydrogenase.,Carbone V, Schofield LR, Zhang Y, Sang C, Dey D, Hannus IM, Martin WF, Sutherland-Smith AJ, Ronimus RS J Biol Chem. 2015 Aug 28;290(35):21690-704. doi: 10.1074/jbc.M115.647461. Epub, 2015 Jul 14. PMID:26175150[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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