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| | <StructureSection load='3q2j' size='340' side='right'caption='[[3q2j]], [[Resolution|resolution]] 2.15Å' scene=''> | | <StructureSection load='3q2j' size='340' side='right'caption='[[3q2j]], [[Resolution|resolution]] 2.15Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3q2j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q2J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3q2j]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3Q2J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3Q2J FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CKI:N-(2-AMINOETHYL)-5-CHLOROISOQUINOLINE-8-SULFONAMIDE'>CKI</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1501Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1j7l|1j7l]], [[1j7i|1j7i]], [[1j7u|1j7u]], [[1l8t|1l8t]], [[2b0q|2b0q]], [[3h8p|3h8p]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CKI:N-(2-AMINOETHYL)-5-CHLOROISOQUINOLINE-8-SULFONAMIDE'>CKI</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Kanamycin_kinase Kanamycin kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.95 2.7.1.95] </span></td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3q2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q2j OCA], [https://pdbe.org/3q2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q2j RCSB], [https://www.ebi.ac.uk/pdbsum/3q2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q2j ProSAT]</span></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=3q2j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3q2j OCA], [https://pdbe.org/3q2j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3q2j RCSB], [https://www.ebi.ac.uk/pdbsum/3q2j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3q2j ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/KKA3_ENTFL KKA3_ENTFL]] Resistance to kanamycin and structurally-related aminoglycosides, including amikacin.
| + | [https://www.uniprot.org/uniprot/KKA3_ENTFL KKA3_ENTFL] Resistance to kanamycin and structurally-related aminoglycosides, including amikacin. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Antibiotic resistance is recognized as a growing healthcare problem. To address this issue, one strategy is to thwart the causal mechanism using an adjuvant in partner with the antibiotic. Aminoglycosides are a class of clinically important antibiotics used for the treatment of serious infections. Their usefulness has been compromised predominantly due to drug inactivation by aminoglycoside-modifying enzymes, such as aminoglycoside phosphotransferases or kinases. These kinases are structurally homologous to eukaryotic Ser/Thr and Tyr protein kinases and it has been shown that some can be inhibited by select protein kinase inhibitors. The aminoglycoside kinase, APH(3')-IIIa, can be inhibited by CKI-7, an ATP-competitive inhibitor for the casein kinase 1. We have determined that CKI-7 is also a moderate inhibitor for the atypical APH(9)-Ia. Here we present the crystal structures of CKI-7-bound APH(3')-IIIa and APH(9)-Ia, the first structures of a eukaryotic protein kinase inhibitor in complex with bacterial kinases. CKI-7 binds to the nucleotide-binding pocket of the enzymes and its binding alters the conformation of the nucleotide-binding loop, the segment homologous to the glycine-rich loop in eukaryotic protein kinases. Comparison of these structures with the CKI-7-bound casein kinase 1 reveals features in the binding pockets that are distinct in the bacterial kinases and could be exploited for the design of a bacterial kinase specific inhibitor. Our results provide evidence that an inhibitor for a subset of APHs can be developed in order to curtail resistance to aminoglycosides.
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| - | | + | |
| - | Crystal structures of two aminoglycoside kinases bound with a eukaryotic protein kinase inhibitor.,Fong DH, Xiong B, Hwang J, Berghuis AM PLoS One. 2011 May 9;6(5):e19589. doi: 10.1371/journal.pone.0019589. PMID:21573013<ref>PMID:21573013</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3q2j" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]] | | *[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]] | + | [[Category: Enterococcus faecalis]] |
| - | [[Category: Kanamycin kinase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Berghuis, A M]] | + | [[Category: Berghuis AM]] |
| - | [[Category: Fong, D H]] | + | [[Category: Fong DH]] |
| - | [[Category: Hwang, J]] | + | [[Category: Hwang J]] |
| - | [[Category: Xiong, B]] | + | [[Category: Xiong B]] |
| - | [[Category: Kinase]]
| + | |
| - | [[Category: Phosphorylation]]
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| - | [[Category: Ser/thr/tyr protein kinase]]
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| - | [[Category: Transferase-transferase inhibitor complex]]
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