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Nat Commun. 2014 Jun 13;5:4068. doi: 10.1038/ncomms5068.

Structural basis for catalysis in a CDP-alcohol phosphotransferase.

Author information

1
1] Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, USA [2].
2
1] Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA [2].
3
New York Consortium on Membrane Protein Structure, New York Structural Biology Center, 89 Convent Avenue, New York, New York 10027, USA.
4
Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, USA.
5
Department of Chemistry and Chemical Biology, Cornell University, NE-CAT, Advanced Photon Source, Argonne, Illinois 60439, USA.
6
Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York 10032, USA.
7
Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.

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.

PMID:
24923293
PMCID:
PMC4098843
DOI:
10.1038/ncomms5068
[Indexed for MEDLINE]
Free PMC Article

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