4dfu

<StructureSection load='4dfu' size='340' side='right' caption='[[4dfu]], [[Resolution|resolution]] 1.98&Aring;' scene=''>

<table><tr><td colspan='2'>[[4dfu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Enterococcus_casseliflavus Enterococcus casseliflavus] and [http://en.wikipedia.org/wiki/Streptomyces_kanamyceticus Streptomyces kanamyceticus]. This structure supersedes the now removed PDB entries and [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3r82 3r82]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DFU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DFU 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=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=QUE:3,5,7,3,4-PENTAHYDROXYFLAVONE'>QUE</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">[[4dbx|4dbx]], [[4de4|4de4]], [[4dfb|4dfb]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APH(2")-Id ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=37734 Enterococcus casseliflavus])</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=4dfu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dfu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4dfu RCSB], [http://www.ebi.ac.uk/pdbsum/4dfu PDBsum]</span></td></tr>

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== Publication Abstract from PubMed ==

Kinase-mediated resistance to antibiotics is a significant clinical challenge. These enzymes share a common protein fold characteristic of Ser/Thr/Tyr protein kinases. We screened 14 antibiotic resistance kinases against 80 chemically diverse protein kinase inhibitors to map resistance kinase chemical space. The screens identified molecules with both broad and narrow inhibition profiles, proving that protein kinase inhibitors offer privileged chemical matter with the potential to block antibiotic resistance. One example is the flavonol quercetin, which inhibited a number of resistance kinases in vitro and in vivo. This activity was rationalized by determination of the crystal structure of the aminoglycoside kinase APH(2'')-IVa in complex with quercetin and its antibiotic substrate kanamycin. Our data demonstrate that protein kinase inhibitors offer chemical scaffolds that can block antibiotic resistance, providing leads for co-drug design.

 

A small molecule discrimination map of the antibiotic resistance kinome.,Shakya T, Stogios PJ, Waglechner N, Evdokimova E, Ejim L, Blanchard JE, McArthur AG, Savchenko A, Wright GD Chem Biol. 2011 Dec 23;18(12):1591-601. PMID:22195561<ref>PMID:22195561</ref>

 

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*[[Phosphotransferase|Phosphotransferase]]

[[Category: Streptomyces kanamyceticus]]

[[Category: Anderson, W F]]

[[Category: Structural genomic]]

[[Category: Dong, A]]

[[Category: Egorova, E]]

[[Category: Evdokimova, E]]

[[Category: Leo, R Di]]

[[Category: Li, H]]

[[Category: Minasov, G]]

[[Category: Savchenko, A]]

[[Category: Shakya, T]]

[[Category: Stogios, P J]]

[[Category: Wright, G D]]

[[Category: Transferase-antibotic-inhibitor complex]]