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| | ==Crystal structure of Archaeoglobus fulgidus IPCT-DIPPS bifunctional membrane protein== | | ==Crystal structure of Archaeoglobus fulgidus IPCT-DIPPS bifunctional membrane protein== |
| - | <StructureSection load='4mnd' size='340' side='right' caption='[[4mnd]], [[Resolution|resolution]] 2.66Å' scene=''> | + | <StructureSection load='4mnd' size='340' side='right'caption='[[4mnd]], [[Resolution|resolution]] 2.66Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4mnd]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MND OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MND FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4mnd]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Archaeoglobus_fulgidus Archaeoglobus fulgidus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MND OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MND FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=LFA:EICOSANE'>LFA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.66Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mnd OCA], [http://pdbe.org/4mnd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mnd RCSB], [http://www.ebi.ac.uk/pdbsum/4mnd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mnd ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LFA:EICOSANE'>LFA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mnd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mnd OCA], [https://pdbe.org/4mnd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mnd RCSB], [https://www.ebi.ac.uk/pdbsum/4mnd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mnd ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DIPPS_ARCFU DIPPS_ARCFU]] Involved in biosynthesis of di-myo-inositol phosphate (DIP), a widespread organic solute in microorganisms adapted to hot environments. Catalyzes the condensation of CTP and L-myo-inositol-1-phosphate into CDP-L-myo-inositol, as well as the biosynthesis of di-myo-inositol-1,3'-phosphate-1'-phosphate (DIPP) from CDP-L-myo-inositol and L-myo-inositol-1-phosphate. The cytidylyltransferase is absolutely specific for CTP and L-myo-inositol-1-P. The DIPP synthase uses only L-myoinositol-1-phosphate as an alcohol acceptor, but CDP-glycerol, as well as CDP-L-myo-inositol and CDP-D-myoinositol, are recognized as alcohol donors.<ref>PMID:17028285</ref> <ref>PMID:17526717</ref> <ref>PMID:21378188</ref> | + | [https://www.uniprot.org/uniprot/DIPPS_ARCFU DIPPS_ARCFU] Involved in biosynthesis of di-myo-inositol phosphate (DIP), a widespread organic solute in microorganisms adapted to hot environments. Catalyzes the condensation of CTP and L-myo-inositol-1-phosphate into CDP-L-myo-inositol, as well as the biosynthesis of di-myo-inositol-1,3'-phosphate-1'-phosphate (DIPP) from CDP-L-myo-inositol and L-myo-inositol-1-phosphate. The cytidylyltransferase is absolutely specific for CTP and L-myo-inositol-1-P. The DIPP synthase uses only L-myoinositol-1-phosphate as an alcohol acceptor, but CDP-glycerol, as well as CDP-L-myo-inositol and CDP-D-myoinositol, are recognized as alcohol donors.<ref>PMID:17028285</ref> <ref>PMID:17526717</ref> <ref>PMID:21378188</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Archer, M]] | + | [[Category: Archaeoglobus fulgidus]] |
| - | [[Category: Borges, N]] | + | [[Category: Large Structures]] |
| - | [[Category: Borshchevskiy, V]] | + | [[Category: Archer M]] |
| - | [[Category: Esteves, A M]] | + | [[Category: Borges N]] |
| - | [[Category: Gordeliy, V]] | + | [[Category: Borshchevskiy V]] |
| - | [[Category: Grudinin, S]] | + | [[Category: Esteves AM]] |
| - | [[Category: Gushchin, I]] | + | [[Category: Gordeliy V]] |
| - | [[Category: Ishchenko, A]] | + | [[Category: Grudinin S]] |
| - | [[Category: Ma, P]] | + | [[Category: Gushchin I]] |
| - | [[Category: Moraes, I]] | + | [[Category: Ishchenko A]] |
| - | [[Category: Nogly, P]] | + | [[Category: Ma P]] |
| - | [[Category: Remeeva, A]] | + | [[Category: Moraes I]] |
| - | [[Category: Round, E]] | + | [[Category: Nogly P]] |
| - | [[Category: Santos, H]] | + | [[Category: Remeeva A]] |
| - | [[Category: Cdp-alcohol phosphotransferase]]
| + | [[Category: Round E]] |
| - | [[Category: Rossmann fold]]
| + | [[Category: Santos H]] |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transmembrane protein]]
| + | |
| Structural highlights
Function
DIPPS_ARCFU Involved in biosynthesis of di-myo-inositol phosphate (DIP), a widespread organic solute in microorganisms adapted to hot environments. Catalyzes the condensation of CTP and L-myo-inositol-1-phosphate into CDP-L-myo-inositol, as well as the biosynthesis of di-myo-inositol-1,3'-phosphate-1'-phosphate (DIPP) from CDP-L-myo-inositol and L-myo-inositol-1-phosphate. The cytidylyltransferase is absolutely specific for CTP and L-myo-inositol-1-P. The DIPP synthase uses only L-myoinositol-1-phosphate as an alcohol acceptor, but CDP-glycerol, as well as CDP-L-myo-inositol and CDP-D-myoinositol, are recognized as alcohol donors.[1] [2] [3]
Publication Abstract from PubMed
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 A resolution. The bifunctional protein dimerizes through the DIPPS domains, each comprising six transmembrane alpha-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.
X-ray structure of a CDP-alcohol phosphatidyltransferase membrane enzyme and insights into its catalytic mechanism.,Nogly P, Gushchin I, Remeeva A, Esteves AM, Borges N, Ma P, Ishchenko A, Grudinin S, Round E, Moraes I, Borshchevskiy V, Santos H, Gordeliy V, Archer M Nat Commun. 2014 Jun 19;5:4169. doi: 10.1038/ncomms5169. PMID:24942835[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Borges N, Goncalves LG, Rodrigues MV, Siopa F, Ventura R, Maycock C, Lamosa P, Santos H. Biosynthetic pathways of inositol and glycerol phosphodiesters used by the hyperthermophile Archaeoglobus fulgidus in stress adaptation. J Bacteriol. 2006 Dec;188(23):8128-35. Epub 2006 Oct 6. PMID:17028285 doi:http://dx.doi.org/10.1128/JB.01129-06
- ↑ Rodrigues MV, Borges N, Henriques M, Lamosa P, Ventura R, Fernandes C, Empadinhas N, Maycock C, da Costa MS, Santos H. Bifunctional CTP:inositol-1-phosphate cytidylyltransferase/CDP-inositol:inositol-1-phosphate transferase, the key enzyme for di-myo-inositol-phosphate synthesis in several (hyper)thermophiles. J Bacteriol. 2007 Aug;189(15):5405-12. Epub 2007 May 25. PMID:17526717 doi:http://dx.doi.org/JB.00465-07
- ↑ Brito JA, Borges N, Vonrhein C, Santos H, Archer M. Crystal Structure of Archaeoglobus fulgidus CTP:Inositol-1-Phosphate Cytidylyltransferase, a Key Enzyme for Di-myo-Inositol-Phosphate Synthesis in (Hyper)Thermophiles. J Bacteriol. 2011 May;193(9):2177-85. Epub 2011 Mar 4. PMID:21378188 doi:10.1128/JB.01543-10
- ↑ Nogly P, Gushchin I, Remeeva A, Esteves AM, 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. 2014 Jun 19;5:4169. doi: 10.1038/ncomms5169. PMID:24942835 doi:http://dx.doi.org/10.1038/ncomms5169
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