5iqa: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 5iqa is ~~ON HOLD until Paper~~ Publication

==Aminoglycoside Phosphotransferase (2'')-Ia (CTD of AAC(6')-Ie/APH(2'')-Ia) in complex with GMPPNP and Magnesium==

== Structural highlights ==

<table><tr><td colspan='2'>[[5iqa]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IQA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IQA 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=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5iqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iqa OCA], [http://pdbe.org/5iqa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iqa RCSB], [http://www.ebi.ac.uk/pdbsum/5iqa PDBsum]</span></td></tr>

</table>

== Function ==

[[http://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.

== 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.

~~Authors:~~ Caldwell, S.J., ~~Berghuis, A~~.M.

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>

~~Description: Aminoglycoside Phosphotransferase (2'')~~-~~Ia (CTD of AAC(6')~~-Ie/~~APH(2'')-Ia) in complex with GMPPNP and Magnesium~~

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

[[Category: ~~Unreleased Structures~~]]

</div>

[[Category: Caldwell, S.J]]

[[Category: ~~Berghuis, A.M~~]]

== References ==

__TOC__

</StructureSection>

[[Category: Berghuis, A M]]

[[Category: Caldwell, S J]]

[[Category: Aminoglycoside]]

[[Category: Antibiotic]]

[[Category: Kinase]]

[[Category: Resistance]]

[[Category: Transferase]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5iqa is ON HOLD  until Paper Publication
+==Aminoglycoside Phosphotransferase (2'')-Ia (CTD of AAC(6')-Ie/APH(2'')-Ia) in complex with GMPPNP and Magnesium==
+<StructureSection load='5iqa' size='340' side='right' caption='[[5iqa]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5iqa]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5IQA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5IQA 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=GNP:PHOSPHOAMINOPHOSPHONIC+ACID-GUANYLATE+ESTER'>GNP</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">[[5iqb|5iqb]], [[5iqc|5iqc]], [[5iqd|5iqd]], [[5iqe|5iqe]], [[5iqf|5iqf]], [[5iqg|5iqg]], [[5iqh|5iqh]], [[5iqi|5iqi]], [[5byl|5byl]]</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=5iqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5iqa OCA], [http://pdbe.org/5iqa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5iqa RCSB], [http://www.ebi.ac.uk/pdbsum/5iqa PDBsum]</span></td></tr>
+</table>
+== Function ==
+[[http://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.
-Authors: Caldwell, S.J., Berghuis, A.M.
+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>
-Description: Aminoglycoside Phosphotransferase (2'')-Ia (CTD of AAC(6')-Ie/APH(2'')-Ia) in complex with GMPPNP and Magnesium
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Caldwell, S.J]]
+<div class="pdbe-citations 5iqa" style="background-color:#fffaf0;"></div>
-[[Category: Berghuis, A.M]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Berghuis, A M]]
+[[Category: Caldwell, S J]]
+[[Category: Aminoglycoside]]
+[[Category: Antibiotic]]
+[[Category: Kinase]]
+[[Category: Resistance]]
+[[Category: Transferase]]