4o6n

Publication Abstract from PubMed

The CDP-alcohol phosphotransferase (CDP-AP) family of integral membrane enzymes catalyses the transfer of a substituted phosphate group from a CDP-linked donor to an alcohol acceptor. This is an essential reaction for phospholipid biosynthesis across all kingdoms of life, and it is catalysed solely by CDP-APs. Here we report the 2.0 A resolution crystal structure of a representative CDP-AP from Archaeoglobus fulgidus. The enzyme (AF2299) is a homodimer, with each protomer consisting of six transmembrane helices and an N-terminal cytosolic domain. A polar cavity within the membrane accommodates the active site, lined with the residues from an absolutely conserved CDP-AP signature motif (D(1)xxD(2)G(1)xxAR...G(2)xxxD(3)xxxD(4)). Structures in the apo, CMP-bound, CDP-bound and CDP-glycerol-bound states define functional roles for each of these eight conserved residues and allow us to propose a sequential, base-catalysed mechanism universal for CDP-APs, in which the fourth aspartate (D4) acts as the catalytic base.

Structural basis for catalysis in a CDP-alcohol phosphotransferase.,Sciara G, Clarke OB, Tomasek D, Kloss B, Tabuso S, Byfield R, Cohn R, Banerjee S, Rajashankar KR, Slavkovic V, Graziano JH, Shapiro L, Mancia F Nat Commun. 2014 Jun 13;5:4068. doi: 10.1038/ncomms5068. PMID:24923293^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.