View source for 5uxd


==Crystal structure of macrolide 2'-phosphotransferase MphH from Brachybacterium faecium in complex with azithromycin==
<StructureSection load='5uxd' size='340' side='right'caption='[[5uxd]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5uxd]] is a 2 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=5UXD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UXD FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.7&#8491;</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=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=5uxd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uxd OCA], [https://pdbe.org/5uxd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uxd RCSB], [https://www.ebi.ac.uk/pdbsum/5uxd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uxd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/C7MEP1_BRAFD C7MEP1_BRAFD] 
<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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5uxd" style="background-color:#fffaf0;"></div>

==See Also==
*[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Brachybacterium faecium DSM 4810]]
[[Category: Large Structures]]
[[Category: Anderson WF]]
[[Category: Savchenko A]]
[[Category: Skarina T]]
[[Category: Stogios PJ]]
[[Category: Wawrzak Z]]
[[Category: Yim V]]