1l8t

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(New page: 200px<br /><applet load="1l8t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l8t, resolution 2.4&Aring;" /> '''Crystal Structure Of ...)
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[[Image:1l8t.jpg|left|200px]]<br /><applet load="1l8t" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1l8t, resolution 2.4&Aring;" />
 
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'''Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex'''<br />
 
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==Overview==
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==Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex==
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The misuse of antibiotics has selected for bacteria that have evolved, mechanisms for evading the effects of these drugs. For aminoglycosides, a, group of clinically important bactericidal antibiotics that target the, A-site of the 16S ribosomal RNA, the most common mode of resistance is, enzyme-catalyzed chemical modification of the drug. While aminoglycosides, are structurally diverse, a single enzyme can confer resistance to many of, these antibiotics. For example, the aminoglycoside kinase APH(3')-IIIa, produced by pathogenic Gram-positive bacteria such as enterococci and, staphylococci, is capable of detoxifying at least 10 distinct, aminoglycosides. Here we describe the crystal structures of APH(3')-IIIa, in complex with ADP and kanamycin A or neomycin B. These structures reveal, that the basis for this enzyme's substrate promiscuity is the presence of, two alternative subsites in the antibiotic binding pocket. Furthermore, comparison between the A-site of the bacterial ribosome and APH(3')-IIIa, shows that mimicry is the second major factor in dictating the substrate, spectrum of APH(3')-IIIa. These results suggest a potential strategy for, drug design aimed at circumventing antibiotic resistance.
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<StructureSection load='1l8t' size='340' side='right'caption='[[1l8t]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1l8t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. The February 2012 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Aminoglycoside Antibiotics'' by David Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2012_2 10.2210/rcsb_pdb/mom_2012_2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L8T FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=1l8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8t OCA], [https://pdbe.org/1l8t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l8t RCSB], [https://www.ebi.ac.uk/pdbsum/1l8t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l8t ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/KKA3_ENTFL KKA3_ENTFL] Resistance to kanamycin and structurally-related aminoglycosides, including amikacin.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l8/1l8t_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=1l8t ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1L8T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis] with MG, ADP and KAN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Kanamycin_kinase Kanamycin kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.95 2.7.1.95] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1L8T OCA].
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*[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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Substrate promiscuity of an aminoglycoside antibiotic resistance enzyme via target mimicry., Fong DH, Berghuis AM, EMBO J. 2002 May 15;21(10):2323-31. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12006485 12006485]
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[[Category: Aminoglycoside Antibiotics]]
[[Category: Enterococcus faecalis]]
[[Category: Enterococcus faecalis]]
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[[Category: Kanamycin kinase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Berghuis, A.M.]]
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[[Category: Berghuis AM]]
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[[Category: Fong, D.H.]]
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[[Category: Fong DH]]
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[[Category: ADP]]
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[[Category: KAN]]
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[[Category: MG]]
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[[Category: transferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 20:22:48 2007''
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Current revision

Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex

PDB ID 1l8t

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