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 with sequence from [ | <table><tr><td colspan='2'>[[5uxc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Brachybacterium_faecium_DSM_4810 Brachybacterium faecium DSM 4810]. 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 [https://proteopedia.org/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><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.72Å</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=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5uxc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uxc OCA], [https://pdbe.org/5uxc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uxc RCSB], [https://www.ebi.ac.uk/pdbsum/5uxc PDBsum], [https://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'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/C7MEP1_BRAFD C7MEP1_BRAFD] | |||
<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: | [[Category: Brachybacterium faecium DSM 4810]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Anderson | [[Category: Anderson WF]] | ||
[[Category: Savchenko A]] | |||
[[Category: Savchenko | [[Category: Skarina T]] | ||
[[Category: Skarina | [[Category: Stogios PJ]] | ||
[[Category: Stogios | [[Category: Wawrzak Z]] | ||
[[Category: Wawrzak | [[Category: Yim V]] | ||
[[Category: Yim | |||
Latest revision as of 10:40, 17 October 2024
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
FunctionPublication 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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