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4k3t
From Proteopedia
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| - | + | ==Crystal structure of glycopeptide hexose oxidase DBV29 complexed with teicoplanin== | |
| - | + | <StructureSection load='4k3t' size='340' side='right' caption='[[4k3t]], [[Resolution|resolution]] 1.93Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[4k3t]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Actinoplanes_teichomyceticus Actinoplanes teichomyceticus] and [http://en.wikipedia.org/wiki/Nonomuraea_sp._atcc_39727 Nonomuraea sp. atcc 39727]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2wdx 2wdx]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K3T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K3T FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=T55:8-METHYLNONANOIC+ACID'>T55</scene>, <scene name='pdbligand=TM9:(2R,3R,4S,5R,6R)-3-AZANYL-6-[BIS(OXIDANYL)METHYL]OXANE-2,4,5-TRIOL'>TM9</scene></td></tr> | ||
| + | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=3FG:(2S)-AMINO(3,5-DIHYDROXYPHENYL)ETHANOIC+ACID'>3FG</scene>, <scene name='pdbligand=3MY:3-CHLORO-D-TYROSINE'>3MY</scene>, <scene name='pdbligand=GHP:(2R)-AMINO(4-HYDROXYPHENYL)ETHANOIC+ACID'>GHP</scene>, <scene name='pdbligand=OMY:(BETAR)-3-CHLORO-BETA-HYDROXY-L-TYROSINE'>OMY</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wdw|2wdw]], [[2wdx|2wdx]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">dbv29 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=93944 Nonomuraea sp. ATCC 39727])</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Alcohol_oxidase Alcohol oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.3.13 1.1.3.13] </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=4k3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k3t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k3t RCSB], [http://www.ebi.ac.uk/pdbsum/4k3t PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | + | </div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Actinoplanes teichomyceticus]] | [[Category: Actinoplanes teichomyceticus]] | ||
[[Category: Alcohol oxidase]] | [[Category: Alcohol oxidase]] | ||
[[Category: Nonomuraea sp. atcc 39727]] | [[Category: Nonomuraea sp. atcc 39727]] | ||
| - | [[Category: Li, T L | + | [[Category: Li, T L]] |
| - | [[Category: Liu, Y C | + | [[Category: Liu, Y C]] |
[[Category: Alpha/beta]] | [[Category: Alpha/beta]] | ||
[[Category: Fad binding]] | [[Category: Fad binding]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
[[Category: Oxidoreductase-antibiotic complex]] | [[Category: Oxidoreductase-antibiotic complex]] | ||
Revision as of 14:51, 21 December 2014
Crystal structure of glycopeptide hexose oxidase DBV29 complexed with teicoplanin
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