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@ARTICLE{Nogly:186128,
author = {Nogly, Przemyslaw and Gushchin, Ivan and Remeeva, Alina and
Esteves, Ana M. and Borges, Nuno and Ma, Pikyee and
Ishchenko, Andrii and Grudinin, Sergei and Round, Ekaterina
and Moraes, Isabel and Borshchevskiy, Valentin and Santos,
Helena and Gordeliy, Valentin and Archer, Margarida},
title = {{X}-ray structure of a {CDP}-alcohol
phosphatidyltransferase membrane enzyme and insights into
its catalytic mechanism},
journal = {Nature Communications},
volume = {5},
issn = {2041-1723},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2015-00216},
pages = {1-10},
year = {2014},
abstract = {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.},
cin = {ICS-6},
ddc = {500},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {452 - Structural Biology (POF2-452)},
pid = {G:(DE-HGF)POF2-452},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000338838500025},
pubmed = {pmid:24942835},
doi = {10.1038/ncomms5169},
url = {https://juser.fz-juelich.de/record/186128},
}