4MND

Crystal structure of Archaeoglobus fulgidus IPCT-DIPPS bifunctional membrane protein

Summary for 4MND

• Entry DOI: 10.2210/pdb4mnd/pdb
• Descriptor: CTP L-myo-inositol-1-phosphate cytidylyltransferase/CDP-L-myo-inositol myo-inositolphosphotransferase, EICOSANE, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: transmembrane protein, rossmann fold, cdp-alcohol phosphotransferase, transferase
• Biological source: Archaeoglobus fulgidus
• Cellular location: Membrane; Multi-pass membrane protein (Potential): O29976
• Total number of polymer chains: 1
• Total formula weight: 54786.91

Authors

Nogly, P.,Gushchin, I.,Remeeva, A.,Esteves, A.M.,Ishchenko, A.,Ma, P.,Grudinin, S.,Borges, N.,Round, E.,Moraes, I.,Borshchevskiy, V.,Santos, H.,Gordeliy, V.,Archer, M. (deposition date: 2013-09-10, release date: 2014-07-02, Last modification date: 2023-09-20)

Primary citation

Nogly, P.,Gushchin, I.,Remeeva, A.,Esteves, A.M.,Borges, N.,Ma, P.,Ishchenko, A.,Grudinin, S.,Round, E.,Moraes, I.,Borshchevskiy, V.,Santos, H.,Gordeliy, V.,Archer, M.
X-ray structure of a CDP-alcohol phosphatidyltransferase membrane enzyme and insights into its catalytic mechanism.
Nat Commun, 5:4169-4169, 2014

PubMed 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 2.65 Å resolution. The bifunctional protein dimerizes through the DIPPS domains, each comprising six transmembrane α-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.

PubMed: 24942835
DOI: 10.1038/ncomms5169

Experimental method

X-RAY DIFFRACTION (2.66 Å)