1l8t

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[[Image:1l8t.jpg|left|200px]]
 
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{{Structure
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==Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex==
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|PDB= 1l8t |SIZE=350|CAPTION= <scene name='initialview01'>1l8t</scene>, resolution 2.4&Aring;
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<StructureSection load='1l8t' size='340' side='right'caption='[[1l8t]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=ADP:ADENOSINE-5&#39;-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>
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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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|ACTIVITY= <span class='plainlinks'>[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] </span>
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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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|GENE=
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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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|DOMAIN=
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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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|RELATEDENTRY=[[1j7i|1J7I]], [[1j7l|1J7L]], [[1j7u|1J7U]]
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1l8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8t OCA], [http://www.ebi.ac.uk/pdbsum/1l8t PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1l8t RCSB]</span>
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== Function ==
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}}
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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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'''Crystal Structure Of 3',5"-Aminoglycoside Phosphotransferase Type IIIa ADP Kanamycin A Complex'''
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==See Also==
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*[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]]
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__TOC__
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==Overview==
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</StructureSection>
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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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[[Category: Aminoglycoside Antibiotics]]
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==About this Structure==
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1L8T is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8T OCA].
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==Reference==
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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://www.ncbi.nlm.nih.gov/pubmed/12006485 12006485]
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[[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: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:59:40 2008''
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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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