4ka6 - Revision history

OCA: Redirecting to 5syi

OCA — Fri, 09 Sep 2016 16:48:53 GMT

Redirecting to 5syi

←Older revision		Revision as of 16:48, 9 September 2016
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-		+	#REDIRECT [[5syi]] This PDB entry is obsolete and replaced by 5syi
-	~~==Structure of D141A variant of B. pseudomallei KatG complexed with INH==~~	+
-	~~<StructureSection load='4ka6' size='340' side='right' caption='~~[[~~4ka6]], [[Resolution\|resolution]] 1.70Å' scene=''>~~	+
-	~~== Structural highlights ==~~	+
-	~~<table><tr><td colspan='2'>[[4ka6~~]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burps Burps]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KA6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KA6 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=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NIZ:PYRIDINE-4-CARBOHYDRAZIDE'>NIZ</scene></td></tr>	+
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ka5\|4ka5]]</td></tr>~~	+
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BPSL2865, katG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272560 BURPS])</td></tr>	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Catalase_peroxidase Catalase peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.21 1.11.1.21] </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=4ka6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ka6 OCA], [http://pdbe.org/4ka6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ka6 RCSB], [http://www.ebi.ac.uk/pdbsum/4ka6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ka6 ProSAT]</span></td></tr>	+
-	~~</table>~~	+
-	~~== Function ==~~	+
-	~~[[http://www.uniprot.org/uniprot/KATG_BURPS KATG_BURPS]] Bifunctional enzyme with both catalase~~ and ~~broad-spectrum peroxidase activity. Displays also NADH oxidase, isoniazid hydrazine lyase and isonicotinoyl-NAD synthase activity.<ref>PMID:15280362</ref>~~	+
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	~~Isonicotinic acid hydrazide (isoniazid or INH) is a front line antitubercular pro-drug that is converted to its active form, isonicotinyl-NAD,~~ by the bacterial catalase-peroxidase KatG. Understanding the role of KatG in the INH activation process has been hampered by a lack of knowledge of the actual drug binding site. In this work, we have investigated the binding of INH in the main access channel of KatG with a combination of molecular dynamics, using an enhanced-sampling technique (metadynamics), X-ray crystallography, and site-directed mutagenesis. The metadynamics simulations show that there are several weak drug binding sites along the access channel. Moreover, the simulations evidence that complete entrance to the heme active site is impeded by an aspartate residue (D141) located above the heme. This has been confirmed by structural and functional analysis of the D141A mutant, leading to the first X-ray crystallography evidence of INH at the heme access channel.	+
-		+
-	Binding of the Antitubercular Pro-Drug Isoniazid in the Heme Access Channel of Catalase-Peroxidase (KatG). A Combined Structural and Metadynamics Investigation.,Vidossich P, Loewen PC, Carpena X, Fiorin G, Fita I, Rovira C J Phys Chem B. 2014 Mar 20;118(11):2924-31. doi: 10.1021/jp4123425. Epub 2014 Mar, 7. PMID:24568093<ref>PMID:24568093</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 4ka6" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
-	~~__TOC__~~	+
-	~~</StructureSection>~~	+
-	~~[[Category: Burps]]~~	+
-	~~[[Category: Catalase peroxidase]]~~	+
-	~~[[Category: Loewen, P C]]~~	+
-	~~[[Category: Catalase-peroxidase]]~~	+
-	~~[[Category: D141a variant]]~~	+
-	~~[[Category: Isoniazid]]~~	+
-	~~[[Category: Katg]]~~	+
-	~~[[Category: Oxidoreductase]]~~	+

OCA at 01:26, 5 August 2016

OCA — Fri, 05 Aug 2016 01:26:26 GMT

←Older revision		Revision as of 01:26, 5 August 2016
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		+
	==Structure of D141A variant of B. pseudomallei KatG complexed with INH==		==Structure of D141A variant of B. pseudomallei KatG complexed with INH==
	<StructureSection load='4ka6' size='340' side='right' caption='[[4ka6]], [[Resolution\|resolution]] 1.70Å' scene=''>		<StructureSection load='4ka6' size='340' side='right' caption='[[4ka6]], [[Resolution\|resolution]] 1.70Å' scene=''>
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	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BPSL2865, katG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272560 BURPS])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BPSL2865, katG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272560 BURPS])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Catalase_peroxidase Catalase peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.21 1.11.1.21] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Catalase_peroxidase Catalase peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.21 1.11.1.21] </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=4ka6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ka6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ka6 RCSB], [http://www.ebi.ac.uk/pdbsum/4ka6 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=4ka6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ka6 OCA], [http://pdbe.org/4ka6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ka6 RCSB], [http://www.ebi.ac.uk/pdbsum/4ka6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ka6 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
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	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 4ka6" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>

OCA at 21:36, 24 December 2014

OCA — Wed, 24 Dec 2014 21:36:00 GMT

←Older revision		Revision as of 21:36, 24 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_4ka6\| PDB=4ka6 \| SCENE= }}~~	+	==Structure of D141A variant of B. pseudomallei KatG complexed with INH==
-	===Structure of D141A variant of B. pseudomallei KatG complexed with INH===	+	<StructureSection load='4ka6' size='340' side='right' caption='[[4ka6]], [[Resolution\|resolution]] 1.70Å' scene=''>
-	~~{{ABSTRACT_PUBMED_24568093}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[4ka6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burps Burps]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KA6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KA6 FirstGlance]. <br>
-	==Function==	+	</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=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NIZ:PYRIDINE-4-CARBOHYDRAZIDE'>NIZ</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[4ka5\|4ka5]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">BPSL2865, katG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=272560 BURPS])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Catalase_peroxidase Catalase peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.21 1.11.1.21] </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=4ka6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ka6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ka6 RCSB], [http://www.ebi.ac.uk/pdbsum/4ka6 PDBsum]</span></td></tr>
		+	</table>
		+	== Function ==
	[[http://www.uniprot.org/uniprot/KATG_BURPS KATG_BURPS]] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity. Displays also NADH oxidase, isoniazid hydrazine lyase and isonicotinoyl-NAD synthase activity.<ref>PMID:15280362</ref>		[[http://www.uniprot.org/uniprot/KATG_BURPS KATG_BURPS]] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity. Displays also NADH oxidase, isoniazid hydrazine lyase and isonicotinoyl-NAD synthase activity.<ref>PMID:15280362</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Isonicotinic acid hydrazide (isoniazid or INH) is a front line antitubercular pro-drug that is converted to its active form, isonicotinyl-NAD, by the bacterial catalase-peroxidase KatG. Understanding the role of KatG in the INH activation process has been hampered by a lack of knowledge of the actual drug binding site. In this work, we have investigated the binding of INH in the main access channel of KatG with a combination of molecular dynamics, using an enhanced-sampling technique (metadynamics), X-ray crystallography, and site-directed mutagenesis. The metadynamics simulations show that there are several weak drug binding sites along the access channel. Moreover, the simulations evidence that complete entrance to the heme active site is impeded by an aspartate residue (D141) located above the heme. This has been confirmed by structural and functional analysis of the D141A mutant, leading to the first X-ray crystallography evidence of INH at the heme access channel.

-	~~==About this Structure==~~	+	Binding of the Antitubercular Pro-Drug Isoniazid in the Heme Access Channel of Catalase-Peroxidase (KatG). A Combined Structural and Metadynamics Investigation.,Vidossich P, Loewen PC, Carpena X, Fiorin G, Fita I, Rovira C J Phys Chem B. 2014 Mar 20;118(11):2924-31. doi: 10.1021/jp4123425. Epub 2014 Mar, 7. PMID:24568093<ref>PMID:24568093</ref>
-	~~[[4ka6]] is a 2 chain structure~~. ~~Full crystallographic information is available from [http://oca~~.~~weizmann~~.ac.il/~~oca-bin/ocashort?id=4KA6 OCA]~~.	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:024568093</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Burps]]
	[[Category: Catalase peroxidase]]		[[Category: Catalase peroxidase]]
-	[[Category: Loewen, P C.]]	+	[[Category: Loewen, P C]]
	[[Category: Catalase-peroxidase]]		[[Category: Catalase-peroxidase]]
	[[Category: D141a variant]]		[[Category: D141a variant]]

OCA at 07:38, 2 April 2014

OCA — Wed, 02 Apr 2014 07:38:35 GMT

←Older revision		Revision as of 07:38, 2 April 2014
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	{{STRUCTURE_4ka6\| PDB=4ka6 \| SCENE= }}		{{STRUCTURE_4ka6\| PDB=4ka6 \| SCENE= }}
	===Structure of D141A variant of B. pseudomallei KatG complexed with INH===		===Structure of D141A variant of B. pseudomallei KatG complexed with INH===
		+	{{ABSTRACT_PUBMED_24568093}}

	==Function==		==Function==
Line 9:		Line 10:

	==Reference==		==Reference==
-	<references group="xtra"/><references/>	+	<ref group="xtra">PMID:024568093</ref><references group="xtra"/><references/>
	[[Category: Catalase peroxidase]]		[[Category: Catalase peroxidase]]
	[[Category: Loewen, P C.]]		[[Category: Loewen, P C.]]

OCA at 09:32, 19 March 2014

OCA — Wed, 19 Mar 2014 09:32:29 GMT

←Older revision		Revision as of 09:32, 19 March 2014
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-	~~'''Unreleased structure'''~~	+	{{STRUCTURE_4ka6\| PDB=4ka6 \| SCENE= }}
		+	===Structure of D141A variant of B. pseudomallei KatG complexed with INH===

-	~~The entry 4ka6 is ON HOLD~~ ~~until Paper Publication~~	+	==Function==
		+	[[http://www.uniprot.org/uniprot/KATG_BURPS KATG_BURPS]] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity. Displays also NADH oxidase, isoniazid hydrazine lyase and isonicotinoyl-NAD synthase activity.<ref>PMID:15280362</ref>

-	~~Authors~~: ~~Loewen, P~~.C.	+	==About this Structure==
		+	[[4ka6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KA6 OCA].

-	~~Description~~: ~~Structure of D141A variant of B~~. ~~pseudomallei KatG complexed with INH~~	+	==Reference==
		+	<references group="xtra"/><references/>
		+	[[Category: Catalase peroxidase]]
		+	[[Category: Loewen, P C.]]
		+	[[Category: Catalase-peroxidase]]
		+	[[Category: D141a variant]]
		+	[[Category: Isoniazid]]
		+	[[Category: Katg]]
		+	[[Category: Oxidoreductase]]

OCA at 11:30, 19 June 2013

OCA — Wed, 19 Jun 2013 11:30:07 GMT

←Older revision		Revision as of 11:30, 19 June 2013
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 4ka6 is ON HOLD	+	The entry 4ka6 is ON HOLD until Paper Publication

	Authors: Loewen, P.C.		Authors: Loewen, P.C.

	Description: Structure of D141A variant of B. pseudomallei KatG complexed with INH		Description: Structure of D141A variant of B. pseudomallei KatG complexed with INH

OCA: Protected "4ka6" [edit=sysop:move=sysop]

OCA — Thu, 02 May 2013 07:13:53 GMT

Protected "4ka6" [edit=sysop:move=sysop]

←Older revision

Revision as of 07:13, 2 May 2013

OCA: New page: '''Unreleased structure''' The entry 4ka6 is ON HOLD Authors: Loewen, P.C. Description: Structure of D141A variant of B. pseudomallei KatG complexed with INH

OCA — Thu, 02 May 2013 07:13:52 GMT

New page: '''Unreleased structure''' The entry 4ka6 is ON HOLD Authors: Loewen, P.C. Description: Structure of D141A variant of B. pseudomallei KatG complexed with INH

New page

'''Unreleased structure'''

The entry 4ka6 is ON HOLD

Authors: Loewen, P.C.

Description: Structure of D141A variant of B. pseudomallei KatG complexed with INH