4gki - Revision history

OCA at 15:49, 14 March 2024

OCA — Thu, 14 Mar 2024 15:49:11 GMT

←Older revision		Revision as of 15:49, 14 March 2024
Line 10:		Line 10:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/B0VD92_ACIBY B0VD92_ACIBY]		[https://www.uniprot.org/uniprot/B0VD92_ACIBY B0VD92_ACIBY]
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Activity of the aminoglycoside phosphotransferase APH(3')-Ia leads to resistance to aminoglycoside antibiotics in pathogenic Gram-negative bacteria, and contributes to the clinical obsolescence of this class of antibiotics. One strategy to rescuing compromised antibiotics such as aminoglycosides is targeting the enzymes conferring resistance with small molecules. Previously we demonstrated that eukaryotic protein kinase (ePK) inhibitors could inhibit APH enzymes, due to the structural similarity between these two enzyme families. However, limited structural information of enzyme-inhibitor complexes hindered interpretation of the results. As well, cross-reactivity of compounds between APHs and ePKs represents an obstacle to their use as aminoglycoside adjuvants to rescue aminoglycoside antibiotic activity. Here, we structurally and functionally characterize inhibition of APH(3')-Ia by three diverse chemical scaffolds - anthrapyrazolone, 4-anilinoquinazoline and pyrazolopyrimidine (PP) - and reveal distinctions in the binding mode of anthrapyrazolone and PP compounds to APH(3')-Ia versus ePKs. Using this observation, we identify PP-derivatives that select against ePKs, attenuate APH(3')-Ia activity and rescue aminoglycoside antibiotic activity against a resistant E. coli strain. The structures presented here and these inhibition studies provide an important opportunity for structure-based design of compounds to target aminoglycoside phosphotransferases for inhibition, potentially overcoming this form of antibiotic resistance.
-
-	Structure-guided optimization of protein kinase inhibitors reverses aminoglycoside antibiotic resistance.,Stogios PJ, Spanogiannopoulos P, Evdokimova E, Egorova O, Shakya T, Todorovic N, Capretta A, Wright GD, Savchenko A Biochem J. 2013 Jun 12. PMID:23758273<ref>PMID:23758273</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 4gki" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
	*[[Phosphotransferase 3D structures\|Phosphotransferase 3D structures]]		*[[Phosphotransferase 3D structures\|Phosphotransferase 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 08:22, 6 December 2023

OCA — Wed, 06 Dec 2023 08:22:58 GMT

←Older revision		Revision as of 08:22, 6 December 2023
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4gki]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii_AYE Acinetobacter baumannii AYE]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GKI FirstGlance]. <br>		<table><tr><td colspan='2'>[[4gki]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii_AYE Acinetobacter baumannii AYE]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GKI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JN:1-TERT-BUTYL-3-(NAPHTHALEN-1-YLMETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>0JN</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 1.88Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JN:1-TERT-BUTYL-3-(NAPHTHALEN-1-YLMETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>0JN</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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=4gki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gki OCA], [https://pdbe.org/4gki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gki RCSB], [https://www.ebi.ac.uk/pdbsum/4gki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gki ProSAT]</span></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=4gki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gki OCA], [https://pdbe.org/4gki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gki RCSB], [https://www.ebi.ac.uk/pdbsum/4gki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gki ProSAT]</span></td></tr>
	</table>		</table>

OCA at 07:01, 26 October 2022

OCA — Wed, 26 Oct 2022 07:01:45 GMT

←Older revision		Revision as of 07:01, 26 October 2022
Line 1:		Line 1:

	==Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor 1-NM-PP1==		==Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor 1-NM-PP1==
-	<StructureSection load='4gki' size='340' side='right' caption='[[4gki]], [[Resolution\|resolution]] 1.88Å' scene=''>	+	<StructureSection load='4gki' size='340' side='right'caption='[[4gki]], [[Resolution\|resolution]] 1.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gki]] is a 12 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Aciby Aciby~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4GKI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gki]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Acinetobacter_baumannii_AYE Acinetobacter baumannii AYE]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GKI FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0JN:1-TERT-BUTYL-3-(NAPHTHALEN-1-YLMETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>0JN</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=NA:~~SODIUM+ION~~'>NA</scene>, <scene name='pdbligand=~~PEG~~:~~DI(HYDROXYETHYL)ETHER~~'>~~PEG~~</scene>~~</td></tr>~~	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0JN:1-TERT-BUTYL-3-(NAPHTHALEN-1-YLMETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>0JN</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=~~MSE~~:~~SELENOMETHIONINE'>MSE</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=4gki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gki OCA], [https://pdbe.org/4gki PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gki RCSB], [https://www.ebi.ac.uk/pdbsum/4gki PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gki ProSAT]</span></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ej7\|4ej7]], [[4feu\|4feu]], [[4fev\|4fev]], [[4few\|4few]], [[4fex\|4fex]], [[4gkh\|4gkh]]</td></tr>	+
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABAYE3578, APHA1-IAB~~ (~~[http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=509173 ACIBY]~~)~~</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=4gki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gki OCA], [~~http~~://pdbe.org/4gki PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4gki RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4gki PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4gki ProSAT]</span></td></tr>	+
	</table>		</table>
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/B0VD92_ACIBY B0VD92_ACIBY]
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 20:

	==See Also==		==See Also==
-	*[[Phosphotransferase\|Phosphotransferase]]	+	*[[Phosphotransferase 3D structures\|Phosphotransferase 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Aciby~~]]	+	[[Category: Acinetobacter baumannii AYE]]
-	[[Category: ~~Kanamycin kinase~~]]	+	[[Category: Large Structures]]
-	[[Category: Anderson~~, W F~~]]	+	[[Category: Anderson WF]]
-	[[Category: ~~Structural genomic~~]]	+	[[Category: Capretta A]]
-	[[Category: ~~Capretta, A~~]]	+	[[Category: Di Leo R]]
-	[[Category: Egorova, O]]	+	[[Category: Egorova O]]
-	[[Category: Evdokimova, E]]	+	[[Category: Evdokimova E]]
-	~~[[Category: Leo, R Di~~]]	+	[[Category: Minasov G]]
-	[[Category: Minasov, G]]	+	[[Category: Savchenko A]]
-	[[Category: Savchenko, A]]	+	[[Category: Shakya T]]
-	[[Category: Shakya, T]]	+	[[Category: Spanogiannopoulos P]]
-	[[Category: Spanogiannopoulos, P]]	+	[[Category: Stogios PJ]]
-	[[Category: Stogios~~, P J~~]]	+	[[Category: Todorovic N]]
-	[[Category: Todorovic, N]]	+	[[Category: Wawrzak Z]]
-	[[Category: Wawrzak, Z]]	+	[[Category: Wright GD]]
-	[[Category: Wright~~, G D]]~~	+
-	~~[[Category: 1-nm-pp1]]~~	+
-	~~[[Category: Alpha/beta protein]]~~	+
-	~~[[Category: Aminoglycoside phosphotransferase]]~~	+
-	~~[[Category: Aminoglycoside]]~~	+
-	~~[[Category: Antibiotic resistance]]~~	+
-	~~[[Category: Bki]]~~	+
-	~~[[Category: Bumped kinase inhibitor]]~~	+
-	~~[[Category: Csgid]]~~	+
-	~~[[Category: Eukaryotic protein kinase-like fold]]~~	+
-	~~[[Category: Gtp]]~~	+
-	~~[[Category: Intracellular]]~~	+
-	~~[[Category: Kanamycin]]~~	+
-	~~[[Category: National institute of allergy and infectious disease]]~~	+
-	~~[[Category: Niaid]]~~	+
-	~~[[Category: Phosphotransferase]]~~	+
-	~~[[Category: Protein kinase inhibitor]]~~	+
-	~~[[Category: Pyrazolopyrimidine]]~~	+
-	~~[[Category: Transferase]]~~	+
-	~~[[Category: Transferase-transferase inhibitor complex~~]]	+

OCA at 07:59, 4 August 2016

OCA — Thu, 04 Aug 2016 07:59:53 GMT

←Older revision		Revision as of 07:59, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor 1-NM-PP1==		==Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor 1-NM-PP1==
	<StructureSection load='4gki' size='340' side='right' caption='[[4gki]], [[Resolution\|resolution]] 1.88Å' scene=''>		<StructureSection load='4gki' size='340' side='right' caption='[[4gki]], [[Resolution\|resolution]] 1.88Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[4gki]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Acinetobacter_baumannii_aye Acinetobacter baumannii aye~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GKI FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[4gki]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Aciby Aciby]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GKI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0JN:1-TERT-BUTYL-3-(NAPHTHALEN-1-YLMETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>0JN</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0JN:1-TERT-BUTYL-3-(NAPHTHALEN-1-YLMETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>0JN</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ej7\|4ej7]], [[4feu\|4feu]], [[4fev\|4fev]], [[4few\|4few]], [[4fex\|4fex]], [[4gkh\|4gkh]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ej7\|4ej7]], [[4feu\|4feu]], [[4fev\|4fev]], [[4few\|4few]], [[4fex\|4fex]], [[4gkh\|4gkh]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABAYE3578, APHA1-IAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=509173 ~~Acinetobacter baumannii AYE~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABAYE3578, APHA1-IAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=509173 ACIBY])</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='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=4gki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gki OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gki RCSB], [http://www.ebi.ac.uk/pdbsum/4gki PDBsum]</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=4gki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gki OCA], [http://pdbe.org/4gki PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gki RCSB], [http://www.ebi.ac.uk/pdbsum/4gki PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gki ProSAT]</span></td></tr>
	</table>		</table>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 4gki" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Acinetobacter baumannii aye~~]]	+	[[Category: Aciby]]
	[[Category: Kanamycin kinase]]		[[Category: Kanamycin kinase]]
	[[Category: Anderson, W F]]		[[Category: Anderson, W F]]

OCA at 11:27, 21 December 2014

OCA — Sun, 21 Dec 2014 11:27:13 GMT

←Older revision		Revision as of 11:27, 21 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4gki\| PDB=4gki \| SCENE= }}~~	+	==Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor 1-NM-PP1==
-	===Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor 1-NM-PP1===	+	<StructureSection load='4gki' size='340' side='right' caption='[[4gki]], [[Resolution\|resolution]] 1.88Å' scene=''>
-	~~{{ABSTRACT_PUBMED_23758273}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[4gki]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Acinetobacter_baumannii_aye Acinetobacter baumannii aye]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GKI FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=0JN:1-TERT-BUTYL-3-(NAPHTHALEN-1-YLMETHYL)-1H-PYRAZOLO[3,4-D]PYRIMIDIN-4-AMINE'>0JN</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=KAN:KANAMYCIN+A'>KAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ej7\|4ej7]], [[4feu\|4feu]], [[4fev\|4fev]], [[4few\|4few]], [[4fex\|4fex]], [[4gkh\|4gkh]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">ABAYE3578, APHA1-IAB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=509173 Acinetobacter baumannii AYE])</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=4gki FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gki OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gki RCSB], [http://www.ebi.ac.uk/pdbsum/4gki PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Activity of the aminoglycoside phosphotransferase APH(3')-Ia leads to resistance to aminoglycoside antibiotics in pathogenic Gram-negative bacteria, and contributes to the clinical obsolescence of this class of antibiotics. One strategy to rescuing compromised antibiotics such as aminoglycosides is targeting the enzymes conferring resistance with small molecules. Previously we demonstrated that eukaryotic protein kinase (ePK) inhibitors could inhibit APH enzymes, due to the structural similarity between these two enzyme families. However, limited structural information of enzyme-inhibitor complexes hindered interpretation of the results. As well, cross-reactivity of compounds between APHs and ePKs represents an obstacle to their use as aminoglycoside adjuvants to rescue aminoglycoside antibiotic activity. Here, we structurally and functionally characterize inhibition of APH(3')-Ia by three diverse chemical scaffolds - anthrapyrazolone, 4-anilinoquinazoline and pyrazolopyrimidine (PP) - and reveal distinctions in the binding mode of anthrapyrazolone and PP compounds to APH(3')-Ia versus ePKs. Using this observation, we identify PP-derivatives that select against ePKs, attenuate APH(3')-Ia activity and rescue aminoglycoside antibiotic activity against a resistant E. coli strain. The structures presented here and these inhibition studies provide an important opportunity for structure-based design of compounds to target aminoglycoside phosphotransferases for inhibition, potentially overcoming this form of antibiotic resistance.

-	~~==About this~~ Structure==	+	Structure-guided optimization of protein kinase inhibitors reverses aminoglycoside antibiotic resistance.,Stogios PJ, Spanogiannopoulos P, Evdokimova E, Egorova O, Shakya T, Todorovic N, Capretta A, Wright GD, Savchenko A Biochem J. 2013 Jun 12. PMID:23758273<ref>PMID:23758273</ref>
-	~~[[4gki]] is a 12 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Acinetobacter_baumannii_aye Acinetobacter baumannii aye]~~. ~~Full crystallographic information is available from [http~~://~~oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=4GKI OCA].~~	+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>

	==See Also==		==See Also==
	*[[Phosphotransferase\|Phosphotransferase]]		*[[Phosphotransferase\|Phosphotransferase]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:023758273</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Acinetobacter baumannii aye]]		[[Category: Acinetobacter baumannii aye]]
	[[Category: Kanamycin kinase]]		[[Category: Kanamycin kinase]]
-	[[Category: Anderson, W F.]]	+	[[Category: Anderson, W F]]
-	[[Category: ~~CSGID, Center for~~ Structural ~~Genomics of Infectious Diseases.~~]]	+	[[Category: Structural genomic]]
-	[[Category: Capretta, A.]]	+	[[Category: Capretta, A]]
-	[[Category: Egorova, O.]]	+	[[Category: Egorova, O]]
-	[[Category: Evdokimova, E.]]	+	[[Category: Evdokimova, E]]
-	[[Category: Leo, R Di.]]	+	[[Category: Leo, R Di]]
-	[[Category: Minasov, G.]]	+	[[Category: Minasov, G]]
-	[[Category: Savchenko, A.]]	+	[[Category: Savchenko, A]]
-	[[Category: Shakya, T.]]	+	[[Category: Shakya, T]]
-	[[Category: Spanogiannopoulos, P.]]	+	[[Category: Spanogiannopoulos, P]]
-	[[Category: Stogios, P J.]]	+	[[Category: Stogios, P J]]
-	[[Category: Todorovic, N.]]	+	[[Category: Todorovic, N]]
-	[[Category: Wawrzak, Z.]]	+	[[Category: Wawrzak, Z]]
-	[[Category: Wright, G D.]]	+	[[Category: Wright, G D]]
	[[Category: 1-nm-pp1]]		[[Category: 1-nm-pp1]]
	[[Category: Alpha/beta protein]]		[[Category: Alpha/beta protein]]
Line 34:		Line 48:
	[[Category: Bki]]		[[Category: Bki]]
	[[Category: Bumped kinase inhibitor]]		[[Category: Bumped kinase inhibitor]]
-	[[Category: Center for structural genomics of infectious disease]]
	[[Category: Csgid]]		[[Category: Csgid]]
	[[Category: Eukaryotic protein kinase-like fold]]		[[Category: Eukaryotic protein kinase-like fold]]

OCA at 19:03, 7 August 2013

OCA — Wed, 07 Aug 2013 19:03:44 GMT

←Older revision		Revision as of 19:03, 7 August 2013
Line 5:		Line 5:
	==About this Structure==		==About this Structure==
	[[4gki]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Acinetobacter_baumannii_aye Acinetobacter baumannii aye]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA].		[[4gki]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Acinetobacter_baumannii_aye Acinetobacter baumannii aye]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA].
		+
		+	==See Also==
		+	*[[Phosphotransferase\|Phosphotransferase]]

	==Reference==		==Reference==

OCA at 07:16, 30 June 2013

OCA — Sun, 30 Jun 2013 07:16:13 GMT

←Older revision		Revision as of 07:16, 30 June 2013
Line 1:		Line 1:
-	[[Image:4gki.png\|left\|200px]]
-
	{{STRUCTURE_4gki\| PDB=4gki \| SCENE= }}		{{STRUCTURE_4gki\| PDB=4gki \| SCENE= }}
-
	===Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor 1-NM-PP1===		===Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor 1-NM-PP1===
		+	{{ABSTRACT_PUBMED_23758273}}

		+	==About this Structure==
		+	[[4gki]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Acinetobacter_baumannii_aye Acinetobacter baumannii aye]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA].

-	==~~About this Structure~~==	+	==Reference==
-	~~[[4gki]] is a 12 chain structure with sequence from [http~~://~~en.wikipedia.org~~/~~wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA].~~	+	<ref group="xtra">PMID:023758273</ref><references group="xtra"/><references/>
-	[[Category: Acinetobacter baumannii]]	+	[[Category: Acinetobacter baumannii aye]]
	[[Category: Kanamycin kinase]]		[[Category: Kanamycin kinase]]
	[[Category: Anderson, W F.]]		[[Category: Anderson, W F.]]

OCA at 06:37, 3 October 2012

OCA — Wed, 03 Oct 2012 06:37:30 GMT

←Older revision		Revision as of 06:37, 3 October 2012
Line 1:		Line 1:
-	[[Image:4gki.~~jpg~~\|left\|200px]]	+	[[Image:4gki.png\|left\|200px]]

	{{STRUCTURE_4gki\| PDB=4gki \| SCENE= }}		{{STRUCTURE_4gki\| PDB=4gki \| SCENE= }}

OCA at 05:43, 5 September 2012

OCA — Wed, 05 Sep 2012 05:43:33 GMT

←Older revision		Revision as of 05:43, 5 September 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:4gki.jpg\|left\|200px]]

-	~~The entry~~ 4gki ~~is ON HOLD~~	+	{{STRUCTURE_4gki\| PDB=4gki \| SCENE= }}

-	Authors: Stogios, P.J., Evdokimova, E., Wawrzak, Z., Minasov, G., Egorova, O., Di Leo, R., Shakya, T., Spanogiannopoulos, P., Todorovic, N., Capretta, A., Wright, G.D., Savchenko, A., Anderson, W.F., Center for Structural Genomics of ~~Infectious Diseases~~ (~~CSGID~~)	+	===Crystal structure of the aminoglycoside phosphotransferase APH(3')-Ia, with substrate kanamycin and small molecule inhibitor 1-NM-PP1===

-	~~Description: Crystal~~ structure of ~~the aminoglycoside~~ phosphotransferase ~~APH(3')~~-~~Ia, with substrate kanamycin~~ and ~~small molecule~~ inhibitor 1-~~NM-PP1~~	+
		+	==About this Structure==
		+	[[4gki]] is a 12 chain structure with sequence from [http://en.wikipedia.org/wiki/Acinetobacter_baumannii Acinetobacter baumannii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GKI OCA].
		+	[[Category: Acinetobacter baumannii]]
		+	[[Category: Kanamycin kinase]]
		+	[[Category: Anderson, W F.]]
		+	[[Category: CSGID, Center for Structural Genomics of Infectious Diseases.]]
		+	[[Category: Capretta, A.]]
		+	[[Category: Egorova, O.]]
		+	[[Category: Evdokimova, E.]]
		+	[[Category: Leo, R Di.]]
		+	[[Category: Minasov, G.]]
		+	[[Category: Savchenko, A.]]
		+	[[Category: Shakya, T.]]
		+	[[Category: Spanogiannopoulos, P.]]
		+	[[Category: Stogios, P J.]]
		+	[[Category: Todorovic, N.]]
		+	[[Category: Wawrzak, Z.]]
		+	[[Category: Wright, G D.]]
		+	[[Category: 1-nm-pp1]]
		+	[[Category: Alpha/beta protein]]
		+	[[Category: Aminoglycoside phosphotransferase]]
		+	[[Category: Aminoglycoside]]
		+	[[Category: Antibiotic resistance]]
		+	[[Category: Bki]]
		+	[[Category: Bumped kinase inhibitor]]
		+	[[Category: Center for structural genomics of infectious disease]]
		+	[[Category: Csgid]]
		+	[[Category: Eukaryotic protein kinase-like fold]]
		+	[[Category: Gtp]]
		+	[[Category: Intracellular]]
		+	[[Category: Kanamycin]]
		+	[[Category: National institute of allergy and infectious disease]]
		+	[[Category: Niaid]]
		+	[[Category: Phosphotransferase]]
		+	[[Category: Protein kinase inhibitor]]
		+	[[Category: Pyrazolopyrimidine]]
		+	[[Category: Transferase]]
		+	[[Category: Transferase-transferase inhibitor complex]]

OCA: Protected "4gki" [edit=sysop:move=sysop]

OCA — Wed, 22 Aug 2012 05:35:52 GMT

Protected "4gki" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:35, 22 August 2012