Structural basis for catalysis in a CDP-alcohol phosphotransferase.

Publication Type:

Journal Article


Nat Commun, Volume 5, p.4068 (2014)


Alcohols, Amino Acid Motifs, Amino Acid Sequence, Archaeal Proteins, Archaeoglobus fulgidus, Binding Sites, Biocatalysis, Catalytic Domain, Models, Molecular, Molecular Sequence Data, Phosphotransferases (Alcohol Group Acceptor), Protein Structure, Tertiary, Sequence Alignment


<p>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 Å 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.</p>

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