View source for 2wdw


==The Native Crystal Structure of the Primary Hexose Oxidase (Dbv29) in Antibiotic A40926 Biosynthesis==
<StructureSection load='2wdw' size='340' side='right'caption='[[2wdw]], [[Resolution|resolution]] 3.21&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2wdw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Nonomuraea_gerenzanensis Nonomuraea gerenzanensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WDW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WDW 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]] 3.21&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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=2wdw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wdw OCA], [https://pdbe.org/2wdw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wdw RCSB], [https://www.ebi.ac.uk/pdbsum/2wdw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wdw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q7WZ62_9ACTN Q7WZ62_9ACTN] 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wd/2wdw_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2wdw ConSurf].
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== Publication Abstract from PubMed ==
In the search for new efficacious antibiotics, biosynthetic engineering offers attractive opportunities to introduce minor alterations to antibiotic structures that may overcome resistance. Dbv29, a flavin-containing oxidase, catalyzes the four-electron oxidation of a vancomycin-like glycopeptide to yield A40926. Structural and biochemical examination of Dbv29 now provides insights into residues that govern flavinylation and activity, protein conformation and reaction mechanism. In particular, the serendipitous discovery of a reaction intermediate in the crystal structure led us to identify an unexpected opportunity to intercept the normal enzyme mechanism at two different points to create new teicoplanin analogs. Using this method, we synthesized families of antibiotic analogs with amidated and aminated lipid chains, some of which showed marked potency and efficacy against multidrug resistant pathogens. This method offers a new strategy for the development of chemical diversity to combat antibacterial resistance.

Interception of teicoplanin oxidation intermediates yields new antimicrobial scaffolds.,Liu YC, Li YS, Lyu SY, Hsu LJ, Chen YH, Huang YT, Chan HC, Huang CJ, Chen GH, Chou CC, Tsai MD, Li TL Nat Chem Biol. 2011 May;7(5):304-9. Epub 2011 Apr 10. PMID:21478878<ref>PMID:21478878</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2wdw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Nonomuraea gerenzanensis]]
[[Category: Chan H-C]]
[[Category: Chen G-H]]
[[Category: Chen Y-H]]
[[Category: Chou C-C]]
[[Category: Huang C-J]]
[[Category: Huang Y-T]]
[[Category: Li T-L]]
[[Category: Li Y-S]]
[[Category: Liu Y-C]]
[[Category: Lyu S-Y]]
[[Category: Tsai M-D]]