5uxc: Difference between revisions
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<StructureSection load='5uxc' size='340' side='right' caption='[[5uxc]], [[Resolution|resolution]] 1.72Å' scene=''> | <StructureSection load='5uxc' size='340' side='right' caption='[[5uxc]], [[Resolution|resolution]] 1.72Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5uxc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UXC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UXC FirstGlance]. <br> | <table><tr><td colspan='2'>[[5uxc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Brafd Brafd]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UXC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5UXC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZIT:AZITHROMYCIN'>ZIT</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZIT:AZITHROMYCIN'>ZIT</scene></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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uxb|5uxb]], [[5uxd|5uxd]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uxb|5uxb]], [[5uxd|5uxd]], [[5uxa|5uxa]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Bfae_22410 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=446465 BRAFD])</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=5uxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uxc OCA], [http://pdbe.org/5uxc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uxc RCSB], [http://www.ebi.ac.uk/pdbsum/5uxc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uxc 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=5uxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uxc OCA], [http://pdbe.org/5uxc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uxc RCSB], [http://www.ebi.ac.uk/pdbsum/5uxc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uxc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The production of antibiotics by microbes in the environment and their use in medicine and agriculture select for existing and emerging resistance. To address this inevitability, prudent development of antibiotic drugs requires careful consideration of resistance evolution. Here, we identify the molecular basis for expanded substrate specificity in MphI, a macrolide kinase (Mph) that does not confer resistance to erythromycin, in contrast to other known Mphs. Using a combination of phylogenetics, drug-resistance phenotypes, and in vitro enzyme assays, we find that MphI and MphK phosphorylate erythromycin poorly resulting in an antibiotic-sensitive phenotype. Using likelihood reconstruction of ancestral sequences and site-saturation combinatorial mutagenesis, supported by Mph crystal structures, we determine that two non-obvious mutations in combination expand the substrate range. This approach should be applicable for studying the functional evolution of any antibiotic resistance enzyme and for evaluating the evolvability of resistance enzymes to new generations of antibiotic scaffolds. | |||
The evolution of substrate discrimination in macrolide antibiotic resistance enzymes.,Pawlowski AC, Stogios PJ, Koteva K, Skarina T, Evdokimova E, Savchenko A, Wright GD Nat Commun. 2018 Jan 9;9(1):112. doi: 10.1038/s41467-017-02680-0. PMID:29317655<ref>PMID:29317655</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5uxc" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Brafd]] | |||
[[Category: Anderson, W F]] | [[Category: Anderson, W F]] | ||
[[Category: Structural genomic]] | [[Category: Structural genomic]] | ||
Revision as of 11:21, 22 February 2018
Crystal structure of macrolide 2'-phosphotransferase MphH from Brachybacterium faecium in complex with GDPCrystal structure of macrolide 2'-phosphotransferase MphH from Brachybacterium faecium in complex with GDP
Structural highlights
Publication Abstract from PubMedThe production of antibiotics by microbes in the environment and their use in medicine and agriculture select for existing and emerging resistance. To address this inevitability, prudent development of antibiotic drugs requires careful consideration of resistance evolution. Here, we identify the molecular basis for expanded substrate specificity in MphI, a macrolide kinase (Mph) that does not confer resistance to erythromycin, in contrast to other known Mphs. Using a combination of phylogenetics, drug-resistance phenotypes, and in vitro enzyme assays, we find that MphI and MphK phosphorylate erythromycin poorly resulting in an antibiotic-sensitive phenotype. Using likelihood reconstruction of ancestral sequences and site-saturation combinatorial mutagenesis, supported by Mph crystal structures, we determine that two non-obvious mutations in combination expand the substrate range. This approach should be applicable for studying the functional evolution of any antibiotic resistance enzyme and for evaluating the evolvability of resistance enzymes to new generations of antibiotic scaffolds. The evolution of substrate discrimination in macrolide antibiotic resistance enzymes.,Pawlowski AC, Stogios PJ, Koteva K, Skarina T, Evdokimova E, Savchenko A, Wright GD Nat Commun. 2018 Jan 9;9(1):112. doi: 10.1038/s41467-017-02680-0. PMID:29317655[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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