This title appears in the Scientific Report :
2014
Please use the identifier:
http://dx.doi.org/10.1038/ncomms5169 in citations.
Please use the identifier: http://hdl.handle.net/2128/24468 in citations.
X-ray structure of a CDP-alcohol phosphatidyltransferase membrane enzyme and insights into its catalytic mechanism
X-ray structure of a CDP-alcohol phosphatidyltransferase membrane enzyme and insights into its catalytic mechanism
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 cataly...
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Personal Name(s): | Nogly, Przemyslaw |
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Gushchin, Ivan / Remeeva, Alina / Esteves, Ana M. / Borges, Nuno / Ma, Pikyee / Ishchenko, Andrii / Grudinin, Sergei / Round, Ekaterina / Moraes, Isabel / Borshchevskiy, Valentin / Santos, Helena / Gordeliy, Valentin (Corresponding Author) / Archer, Margarida | |
Contributing Institute: |
Strukturbiochemie; ICS-6 |
Published in: | Nature Communications, 5 (2014) S. 1-10 |
Imprint: |
London
Nature Publishing Group
2014
|
DOI: |
10.1038/ncomms5169 |
PubMed ID: |
24942835 |
Document Type: |
Journal Article |
Research Program: |
Structural Biology |
Link: |
OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://hdl.handle.net/2128/24468 in citations.
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. |