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| | ==Crystal structure of rifampin phosphotransferase RPH-Lm from Listeria monocytogenes in complex with rifampin== | | ==Crystal structure of rifampin phosphotransferase RPH-Lm from Listeria monocytogenes in complex with rifampin== |
| - | <StructureSection load='5fbt' size='340' side='right' caption='[[5fbt]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='5fbt' size='340' side='right'caption='[[5fbt]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5fbt]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FBT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FBT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5fbt]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Listeria_monocytogenes_serotype_4b_str._F2365 Listeria monocytogenes serotype 4b str. F2365]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FBT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FBT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5WQ:RIFAMPIN'>5WQ</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</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]] 2.702Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fbs|5fbs]], [[5fbu|5fbu]]</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=5fbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fbt OCA], [https://pdbe.org/5fbt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fbt RCSB], [https://www.ebi.ac.uk/pdbsum/5fbt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fbt 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=5fbt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fbt OCA], [http://pdbe.org/5fbt PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fbt RCSB], [http://www.ebi.ac.uk/pdbsum/5fbt PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/RPH_LISMF RPH_LISMF] Catalyzes the phosphorylation of rifampicin, also known as rifampin (RIF), leading to its inactivation (PubMed:24778229, PubMed:27001859, PubMed:27103605). Confers high level resistance to a variety of clinically used rifamycin antibiotics (PubMed:24778229). Does not show phosphoenolpyruvate (PEP) synthase activity (PubMed:24778229).<ref>PMID:24778229</ref> <ref>PMID:27001859</ref> <ref>PMID:27103605</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: Anderson, W F]] | + | [[Category: Large Structures]] |
| - | [[Category: Structural genomic]] | + | [[Category: Listeria monocytogenes serotype 4b str. F2365]] |
| - | [[Category: Savchenko, A]] | + | [[Category: Anderson WF]] |
| - | [[Category: Skarina, T]] | + | [[Category: Savchenko A]] |
| - | [[Category: Stogios, P J]] | + | [[Category: Skarina T]] |
| - | [[Category: Wawrzak, Z]] | + | [[Category: Stogios PJ]] |
| - | [[Category: Yim, V]] | + | [[Category: Wawrzak Z]] |
| - | [[Category: Antibiotic resistance]]
| + | [[Category: Yim V]] |
| - | [[Category: Atp grasp domain]]
| + | |
| - | [[Category: Csgid]]
| + | |
| - | [[Category: Phosphohistidine domain]]
| + | |
| - | [[Category: Phosphotransferase]]
| + | |
| - | [[Category: Rifampin]]
| + | |
| - | [[Category: Rifamycin]]
| + | |
| - | [[Category: Transferase-antibiotic complex]]
| + | |
| Structural highlights
Function
RPH_LISMF Catalyzes the phosphorylation of rifampicin, also known as rifampin (RIF), leading to its inactivation (PubMed:24778229, PubMed:27001859, PubMed:27103605). Confers high level resistance to a variety of clinically used rifamycin antibiotics (PubMed:24778229). Does not show phosphoenolpyruvate (PEP) synthase activity (PubMed:24778229).[1] [2] [3]
Publication Abstract from PubMed
Rifampin (RIF) phosphotransferase (RPH) confers antibiotic resistance by conversion of RIF and ATP, to inactive phospho-RIF, AMP and Pi. Here we present the crystal structure of RPH from Listeria monocytogenes (RPH-Lm), which reveals that the enzyme is comprised of three domains: two substrate-binding domains (ATP-grasp and RIF-binding domains); and a smaller phosphate-carrying His swivel domain. Using solution small-angle X-ray scattering and mutagenesis, we reveal a mechanism where the swivel domain transits between the spatially distinct substrate-binding sites during catalysis. RPHs are previously uncharacterized dikinases that are widespread in environmental and pathogenic bacteria. These enzymes are members of a large unexplored group of bacterial enzymes with substrate affinities that have yet to be fully explored. Such an enzymatically complex mechanism of antibiotic resistance augments the spectrum of strategies used by bacteria to evade antimicrobial compounds.
Rifampin phosphotransferase is an unusual antibiotic resistance kinase.,Stogios PJ, Cox G, Spanogiannopoulos P, Pillon MC, Waglechner N, Skarina T, Koteva K, Guarne A, Savchenko A, Wright GD Nat Commun. 2016 Apr 22;7:11343. doi: 10.1038/ncomms11343. PMID:27103605[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Spanogiannopoulos P, Waglechner N, Koteva K, Wright GD. A rifamycin inactivating phosphotransferase family shared by environmental and pathogenic bacteria. Proc Natl Acad Sci U S A. 2014 May 13;111(19):7102-7. PMID:24778229 doi:10.1073/pnas.1402358111
- ↑ Qi X, Lin W, Ma M, Wang C, He Y, He N, Gao J, Zhou H, Xiao Y, Wang Y, Zhang P. Structural basis of rifampin inactivation by rifampin phosphotransferase. Proc Natl Acad Sci U S A. 2016 Mar 21. pii: 201523614. PMID:27001859 doi:http://dx.doi.org/10.1073/pnas.1523614113
- ↑ Stogios PJ, Cox G, Spanogiannopoulos P, Pillon MC, Waglechner N, Skarina T, Koteva K, Guarne A, Savchenko A, Wright GD. Rifampin phosphotransferase is an unusual antibiotic resistance kinase. Nat Commun. 2016 Apr 22;7:11343. doi: 10.1038/ncomms11343. PMID:27103605 doi:http://dx.doi.org/10.1038/ncomms11343
- ↑ Stogios PJ, Cox G, Spanogiannopoulos P, Pillon MC, Waglechner N, Skarina T, Koteva K, Guarne A, Savchenko A, Wright GD. Rifampin phosphotransferase is an unusual antibiotic resistance kinase. Nat Commun. 2016 Apr 22;7:11343. doi: 10.1038/ncomms11343. PMID:27103605 doi:http://dx.doi.org/10.1038/ncomms11343
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