4dtb: Difference between revisions
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==Crystal Structure of F95Y Aminoglycoside-2''-Phosphotransferase Type IVa in Complex with Guanosine== | ==Crystal Structure of F95Y Aminoglycoside-2''-Phosphotransferase Type IVa in Complex with Guanosine== | ||
<StructureSection load='4dtb' size='340' side='right' caption='[[4dtb]], [[Resolution|resolution]] 2.10Å' scene=''> | <StructureSection load='4dtb' size='340' side='right'caption='[[4dtb]], [[Resolution|resolution]] 2.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4dtb]] is a 2 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4dtb]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Enterococcus_casseliflavus Enterococcus casseliflavus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DTB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DTB 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=GMP:GUANOSINE'>GMP</scene> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GMP:GUANOSINE'>GMP</scene></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=4dtb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dtb OCA], [https://pdbe.org/4dtb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dtb RCSB], [https://www.ebi.ac.uk/pdbsum/4dtb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dtb ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/O68183_ENTCA O68183_ENTCA]] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[Phosphotransferase|Phosphotransferase]] | *[[Phosphotransferase 3D structures|Phosphotransferase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Enterococcus casseliflavus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Berghuis AM]] | ||
[[Category: | [[Category: Shi K]] | ||
Revision as of 11:37, 21 September 2022
Crystal Structure of F95Y Aminoglycoside-2-Phosphotransferase Type IVa in Complex with GuanosineCrystal Structure of F95Y Aminoglycoside-2-Phosphotransferase Type IVa in Complex with Guanosine
Structural highlights
FunctionPublication Abstract from PubMedEnzymatic phosphorylation through a family of enzymes called aminoglycoside O-phosphotransferases (APHs) is a major mechanism by which bacteria confer resistance to aminoglycoside antibiotics. Members of the APH(2) subfamily are of particular clinical interest because of their prevalence in pathogenic strains and their broad substrate spectra. APH(2) enzymes display differential preferences between ATP or GTP as the phosphate donor, with aminoglycoside 2-phosphotransferase IVa (APH(2)-IVa) being a member that utilizes both nucleotides at comparable efficiencies. We report here four crystal structures of APH(2)-IVa, two of the wild type enzyme and two of single amino acid mutants, each in complex with either adenosine or guanosine. Together, these structures afford a detailed look at the nucleoside-binding site architecture for this enzyme and reveal key elements that confer dual nucleotide specificity, including a solvent network in the interior of the nucleoside-binding pocket and the conformation of an interdomain linker loop. Steady state kinetic studies, as well as sequence and structural comparisons with members of the APH(2) subfamily and other aminoglycoside kinases, rationalize the different substrate preferences for these enzymes. Finally, despite poor overall sequence similarity and structural homology, analysis of the nucleoside-binding pocket of APH(2)-IVa shows a striking resemblance to that of eukaryotic casein kinase 2 (CK2), which also exhibits dual nucleotide specificity. These results, in complement with the multitude of existing inhibitors against CK2, can serve as a structural basis for the design of nucleotide-competitive inhibitors against clinically relevant APH enzymes. Structural Basis for Dual Nucleotide Selectivity of Aminoglycoside 2-Phosphotransferase IVa Provides Insight on Determinants of Nucleotide Specificity of Aminoglycoside Kinases.,Shi K, Berghuis AM J Biol Chem. 2012 Apr 13;287(16):13094-102. Epub 2012 Feb 24. PMID:22371504[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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