4O6M

Structure of AF2299, a CDP-alcohol phosphotransferase (CMP-bound)

Summary for 4O6M

• Entry DOI: 10.2210/pdb4o6m/pdb
• Related: 4O6N
• Descriptor: AF2299, a CDP-alcohol phosphotransferase, CALCIUM ION, [(Z)-octadec-9-enyl] (2R)-2,3-bis(oxidanyl)propanoate, ... (6 entities in total)
• Functional Keywords: cdp-alcohol phosphotransferase, membrane protein, structural genomics, psi-biology, new york consortium on membrane protein structure, nycomps, transferase
• Biological source: Archaeoglobus fulgidus
• Total number of polymer chains: 2
• Total formula weight: 94250.31

Authors

Clarke, O.B.,Sciara, G.,Tomasek, D.,Banerjee, S.,Rajashankar, K.R.,Shapiro, L.,Mancia, F.,New York Consortium on Membrane Protein Structure (NYCOMPS) (deposition date: 2013-12-22, release date: 2014-05-14, Last modification date: 2024-02-28)

Primary citation

Sciara, G.,Clarke, O.B.,Tomasek, D.,Kloss, B.,Tabuso, S.,Byfield, R.,Cohn, R.,Banerjee, S.,Rajashankar, K.R.,Slavkovic, V.,Graziano, J.H.,Shapiro, L.,Mancia, F.
Structural basis for catalysis in a CDP-alcohol phosphotransferase.
Nat Commun, 5:4068-4068, 2014

PubMed Abstract: 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.

PubMed: 24923293
DOI: 10.1038/ncomms5068

Experimental method

X-RAY DIFFRACTION (1.901 Å)