5iqb: Difference between revisions
New page: '''Unreleased structure''' The entry 5iqb is ON HOLD until Paper Publication Authors: Caldwell, S.J., Berghuis, A.M. Description: Aminoglycoside Phosphotransferase (2'')-Ia (CTD of AAC... |
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==Aminoglycoside Phosphotransferase (2'')-Ia (CTD of AAC(6')-Ie/APH(2'')-Ia) in complex with GMPPNP, Magnesium, and Kanamycin A== | |||
<StructureSection load='5iqb' size='340' side='right'caption='[[5iqb]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5iqb]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5IQB FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</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=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5iqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iqb OCA], [https://pdbe.org/5iqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5iqb RCSB], [https://www.ebi.ac.uk/pdbsum/5iqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5iqb ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AACA_STAAU AACA_STAAU] Resistance to gentamicin, tobramycin, and kanamycin. Tobramycin and kanamycin resistance is due to the ACC activity, specified by N-terminal region, and the gentamicin resistance is due to the APH activity encoded by the C-terminal region of the protein. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
APH(2'')-Ia is a widely disseminated resistance factor frequently found in clinical isolates of Staphylococcus aureus and pathogenic enterococci, where it is constitutively expressed. APH(2'')-Ia confers high-level resistance to gentamicin and related aminoglycosides through phosphorylation of the antibiotic using guanosine triphosphate (GTP) as phosphate donor. We have determined crystal structures of the APH(2'')-Ia in complex with GTP analogs, guanosine diphosphate, and aminoglycosides. These structures collectively demonstrate that aminoglycoside binding to the GTP-bound kinase drives conformational changes that bring distant regions of the protein into contact. These changes in turn drive a switch of the triphosphate cofactor from an inactive, stabilized conformation to a catalytically competent active conformation. This switch has not been previously reported for antibiotic kinases or for the structurally related eukaryotic protein kinases. This catalytic triphosphate switch presents a means by which the enzyme can curtail wasteful hydrolysis of GTP in the absence of aminoglycosides, providing an evolutionary advantage to this enzyme. | |||
Antibiotic Binding Drives Catalytic Activation of Aminoglycoside Kinase APH(2'')-Ia.,Caldwell SJ, Huang Y, Berghuis AM Structure. 2016 May 5. pii: S0969-2126(16)30038-7. doi:, 10.1016/j.str.2016.04.002. PMID:27161980<ref>PMID:27161980</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5iqb" style="background-color:#fffaf0;"></div> | ||
[[Category: Berghuis | == References == | ||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Staphylococcus aureus]] | |||
[[Category: Berghuis AM]] | |||
[[Category: Caldwell SJ]] | |||