TY  - JOUR
AU  - Nogly, Przemyslaw
AU  - Gushchin, Ivan
AU  - Remeeva, Alina
AU  - Esteves, Ana M.
AU  - Borges, Nuno
AU  - Ma, Pikyee
AU  - Ishchenko, Andrii
AU  - Grudinin, Sergei
AU  - Round, Ekaterina
AU  - Moraes, Isabel
AU  - Borshchevskiy, Valentin
AU  - Santos, Helena
AU  - Gordeliy, Valentin
AU  - Archer, Margarida
TI  - X-ray structure of a CDP-alcohol phosphatidyltransferase membrane enzyme and insights into its catalytic mechanism
JO  - Nature Communications
VL  - 5
SN  - 2041-1723
CY  - London
PB  - Nature Publishing Group
M1  - FZJ-2015-00216
SP  - 1-10
PY  - 2014
AB  - Phospholipids have major roles in the structure and function of all cell membranes. Most integral membrane proteins from the large CDP-alcohol phosphatidyltransferase family are involved in phospholipid biosynthesis across the three domains of life. They share a conserved sequence pattern and catalyse the displacement of CMP from a CDP-alcohol by a second alcohol. Here we report the crystal structure of a bifunctional enzyme comprising a cytoplasmic nucleotidyltransferase domain (IPCT) fused with a membrane CDP-alcohol phosphotransferase domain (DIPPS) at 2.65Å resolution. The bifunctional protein dimerizes through the DIPPS domains, each comprising six transmembrane a-helices. The active site cavity is hydrophilic and widely open to the cytoplasm with a magnesium ion surrounded by four highly conserved aspartate residues from helices TM2 and TM3. We show that magnesium is essential for the enzymatic activity and is involved in catalysis. Substrates docking is validated by mutagenesis studies, and a structure-based catalytic mechanism is proposed.
LB  - PUB:(DE-HGF)16
UR  - <Go to ISI:>//WOS:000338838500025
C6  - pmid:24942835
DO  - DOI:10.1038/ncomms5169
UR  - https://juser.fz-juelich.de/record/186128
ER  -