1l8t

<table><tr><td colspan='2'>[[1l8t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"enterococcus_proteiformis"_thiercelin_and_jouhaud_1903 "enterococcus proteiformis" thiercelin and jouhaud 1903]. The February 2012 RCSB PDB [http://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 [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1L8T FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1j7i|1j7i]], [[1j7l|1j7l]], [[1j7u|1j7u]]</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></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=1l8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8t OCA], [http://pdbe.org/1l8t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1l8t RCSB], [http://www.ebi.ac.uk/pdbsum/1l8t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1l8t ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/KKA3_ENTFL KKA3_ENTFL]] Resistance to kanamycin and structurally-related aminoglycosides, including amikacin.

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== Publication Abstract from PubMed ==

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.

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:12006485<ref>PMID:12006485</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 1l8t" style="background-color:#fffaf0;"></div>

*[[Phosphotransferase|Phosphotransferase]]

[[Category: Enterococcus proteiformis thiercelin and jouhaud 1903]]

[[Category: Kanamycin kinase]]

[[Category: Berghuis, A M]]

[[Category: Fong, D H]]

[[Category: Transferase]]