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| | ==Integral membrane protein lipooligosaccharide phosphoethanolamine transferase A (EptA) from Neisseria meningitidis== | | ==Integral membrane protein lipooligosaccharide phosphoethanolamine transferase A (EptA) from Neisseria meningitidis== |
| - | <StructureSection load='5fgn' size='340' side='right' caption='[[5fgn]], [[Resolution|resolution]] 2.75Å' scene=''> | + | <StructureSection load='5fgn' size='340' side='right'caption='[[5fgn]], [[Resolution|resolution]] 2.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5fgn]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Neimi Neimi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FGN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FGN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5fgn]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Neisseria_meningitidis_serogroup_B Neisseria meningitidis serogroup B]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FGN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BGL:B-2-OCTYLGLUCOSIDE'>BGL</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.75Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4kav|4kav]], [[4kay|4kay]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGL:B-2-OCTYLGLUCOSIDE'>BGL</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NMB1638 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=491 NEIMI])</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=5fgn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fgn OCA], [https://pdbe.org/5fgn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fgn RCSB], [https://www.ebi.ac.uk/pdbsum/5fgn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fgn ProSAT]</span></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=5fgn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fgn OCA], [http://pdbe.org/5fgn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fgn RCSB], [http://www.ebi.ac.uk/pdbsum/5fgn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fgn ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q7DD94_NEIMB Q7DD94_NEIMB] |
| | <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: Neimi]] | + | [[Category: Large Structures]] |
| - | [[Category: Anandan, A]] | + | [[Category: Neisseria meningitidis serogroup B]] |
| - | [[Category: Vrielink, A]] | + | [[Category: Anandan A]] |
| - | [[Category: Endotoxin biosynthesis]] | + | [[Category: Vrielink A]] |
| - | [[Category: Epta]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Phosphoethanolamine transferase]]
| + | |
| - | [[Category: Phosphotransferase]]
| + | |
| - | [[Category: Polymixin resistance]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
Q7DD94_NEIMB
Publication Abstract from PubMed
Multidrug-resistant (MDR) gram-negative bacteria have increased the prevalence of fatal sepsis in modern times. Colistin is a cationic antimicrobial peptide (CAMP) antibiotic that permeabilizes the bacterial outer membrane (OM) and has been used to treat these infections. The OM outer leaflet is comprised of endotoxin containing lipid A, which can be modified to increase resistance to CAMPs and prevent clearance by the innate immune response. One type of lipid A modification involves the addition of phosphoethanolamine to the 1 and 4' headgroup positions by phosphoethanolamine transferases. Previous structural work on a truncated form of this enzyme suggested that the full-length protein was required for correct lipid substrate binding and catalysis. We now report the crystal structure of a full-length lipid A phosphoethanolamine transferase from Neisseria meningitidis, determined to 2.75-A resolution. The structure reveals a previously uncharacterized helical membrane domain and a periplasmic facing soluble domain. The domains are linked by a helix that runs along the membrane surface interacting with the phospholipid head groups. Two helices located in a periplasmic loop between two transmembrane helices contain conserved charged residues and are implicated in substrate binding. Intrinsic fluorescence, limited proteolysis, and molecular dynamics studies suggest the protein may sample different conformational states to enable the binding of two very different- sized lipid substrates. These results provide insights into the mechanism of endotoxin modification and will aid a structure-guided rational drug design approach to treating multidrug-resistant bacterial infections.
Structure of a lipid A phosphoethanolamine transferase suggests how conformational changes govern substrate binding.,Anandan A, Evans GL, Condic-Jurkic K, O'Mara ML, John CM, Phillips NJ, Jarvis GA, Wills SS, Stubbs KA, Moraes I, Kahler CM, Vrielink A Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2218-2223. doi:, 10.1073/pnas.1612927114. Epub 2017 Feb 13. PMID:28193899[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Anandan A, Evans GL, Condic-Jurkic K, O'Mara ML, John CM, Phillips NJ, Jarvis GA, Wills SS, Stubbs KA, Moraes I, Kahler CM, Vrielink A. Structure of a lipid A phosphoethanolamine transferase suggests how conformational changes govern substrate binding. Proc Natl Acad Sci U S A. 2017 Feb 28;114(9):2218-2223. doi:, 10.1073/pnas.1612927114. Epub 2017 Feb 13. PMID:28193899 doi:http://dx.doi.org/10.1073/pnas.1612927114
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