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[[ | ==Crystal Structure of Aminoglycoside-2''-Phosphotransferase Type IVa Kanamycin A Complex== | ||
<StructureSection load='3sg9' size='340' side='right' caption='[[3sg9]], [[Resolution|resolution]] 2.15Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3sg9]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Enterococcus_casseliflavus Enterococcus casseliflavus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SG9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SG9 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></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=3sg9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sg9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sg9 RCSB], [http://www.ebi.ac.uk/pdbsum/3sg9 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Aminoglycoside 2''-phosphotransferase IVa [APH(2'')-IVa] is a member of a family of bacterial enzymes responsible for medically relevant resistance to antibiotics. APH(2'')-IVa confers high-level resistance against several clinically used aminoglycoside antibiotics in various pathogenic Enterococcus species by phosphorylating the drug, thereby preventing it from binding to its ribosomal target and producing a bactericidal effect. We describe here three crystal structures of APH(2'')-IVa, one in its apo form and two in complex with a bound antibiotic, tobramycin and kanamycin A. The apo structure was refined to a resolution of 2.05 A, and the APH(2'')-IVa structures with tobramycin and kanamycin A bound were refined to resolutions of 1.80 and 2.15 A, respectively. Comparison among the structures provides insight concerning the substrate selectivity of this enzyme. In particular, conformational changes upon substrate binding, involving rotational shifts of two distinct segments of the enzyme, are observed. These substrate-induced shifts may also rationalize the altered substrate preference of APH(2'')-IVa in comparison to those of other members of the APH(2'') subfamily, which are structurally closely related. Finally, analysis of the interactions between the enzyme and aminoglycoside reveals a distinct binding mode as compared to the intended ribosomal target. The differences in the pattern of interactions can be utilized as a structural basis for the development of improved aminoglycosides that are not susceptible to these resistance factors. | |||
Crystal Structures of Antibiotic-Bound Complexes of Aminoglycoside 2''-Phosphotransferase IVa Highlight the Diversity in Substrate Binding Modes among Aminoglycoside Kinases.,Shi K, Houston DR, Berghuis AM Biochemistry. 2011 Jun 27. PMID:21678960<ref>PMID:21678960</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Phosphotransferase|Phosphotransferase]] | *[[Phosphotransferase|Phosphotransferase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Enterococcus casseliflavus]] | [[Category: Enterococcus casseliflavus]] | ||
[[Category: Berghuis, A M | [[Category: Berghuis, A M]] | ||
[[Category: Houston, D R | [[Category: Houston, D R]] | ||
[[Category: Shi, K | [[Category: Shi, K]] | ||
[[Category: Aminoglycoside]] | [[Category: Aminoglycoside]] | ||
[[Category: Antibiotic resistance enzyme]] | [[Category: Antibiotic resistance enzyme]] | ||
Revision as of 14:32, 9 December 2014
Crystal Structure of Aminoglycoside-2-Phosphotransferase Type IVa Kanamycin A ComplexCrystal Structure of Aminoglycoside-2-Phosphotransferase Type IVa Kanamycin A Complex
Structural highlights
Publication Abstract from PubMedAminoglycoside 2-phosphotransferase IVa [APH(2)-IVa] is a member of a family of bacterial enzymes responsible for medically relevant resistance to antibiotics. APH(2)-IVa confers high-level resistance against several clinically used aminoglycoside antibiotics in various pathogenic Enterococcus species by phosphorylating the drug, thereby preventing it from binding to its ribosomal target and producing a bactericidal effect. We describe here three crystal structures of APH(2)-IVa, one in its apo form and two in complex with a bound antibiotic, tobramycin and kanamycin A. The apo structure was refined to a resolution of 2.05 A, and the APH(2)-IVa structures with tobramycin and kanamycin A bound were refined to resolutions of 1.80 and 2.15 A, respectively. Comparison among the structures provides insight concerning the substrate selectivity of this enzyme. In particular, conformational changes upon substrate binding, involving rotational shifts of two distinct segments of the enzyme, are observed. These substrate-induced shifts may also rationalize the altered substrate preference of APH(2)-IVa in comparison to those of other members of the APH(2) subfamily, which are structurally closely related. Finally, analysis of the interactions between the enzyme and aminoglycoside reveals a distinct binding mode as compared to the intended ribosomal target. The differences in the pattern of interactions can be utilized as a structural basis for the development of improved aminoglycosides that are not susceptible to these resistance factors. Crystal Structures of Antibiotic-Bound Complexes of Aminoglycoside 2-Phosphotransferase IVa Highlight the Diversity in Substrate Binding Modes among Aminoglycoside Kinases.,Shi K, Houston DR, Berghuis AM Biochemistry. 2011 Jun 27. PMID:21678960[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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