6geq - Revision history

OCA at 17:19, 14 August 2019

OCA — Wed, 14 Aug 2019 17:19:07 GMT

←Older revision		Revision as of 17:19, 14 August 2019
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	<StructureSection load='6geq' size='340' side='right'caption='[[6geq]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='6geq' size='340' side='right'caption='[[6geq]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6geq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GEQ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6geq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycto Mycto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GEQ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EW5:1-phenyl-3-pyridin-4-yl-~{N}-(pyridin-4-ylmethyl)pyrazole-4-carboxamide'>EW5</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EW5:1-phenyl-3-pyridin-4-yl-~{N}-(pyridin-4-ylmethyl)pyrazole-4-carboxamide'>EW5</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">cyp121, MT2336 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83331 MYCTO])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mycocyclosin_synthase Mycocyclosin synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.21.9 1.14.21.9] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mycocyclosin_synthase Mycocyclosin synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.21.9 1.14.21.9] </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=6geq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6geq OCA], [http://pdbe.org/6geq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6geq RCSB], [http://www.ebi.ac.uk/pdbsum/6geq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6geq ProSAT]</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=6geq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6geq OCA], [http://pdbe.org/6geq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6geq RCSB], [http://www.ebi.ac.uk/pdbsum/6geq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6geq ProSAT]</span></td></tr>
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	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/CP121_MYCTO CP121_MYCTO]] Catalyzes C-C bond formation between the carbons ortho to the phenolic hydroxyl of cyclo(L-tyr-L-tyr) (cYY) producing mycocyclosin. Can also use cyclo(L-Tyr-L-Phe) (cYF), cyclo(L-Tyr-L-Trp) (cYW) and cyclo(L-Tyr-L-3,4-dihydroxyphenylalanine) (cY-DOPA) as substrate (By similarity).		[[http://www.uniprot.org/uniprot/CP121_MYCTO CP121_MYCTO]] Catalyzes C-C bond formation between the carbons ortho to the phenolic hydroxyl of cyclo(L-tyr-L-tyr) (cYY) producing mycocyclosin. Can also use cyclo(L-Tyr-L-Phe) (cYF), cyclo(L-Tyr-L-Trp) (cYW) and cyclo(L-Tyr-L-3,4-dihydroxyphenylalanine) (cY-DOPA) as substrate (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The emergence of untreatable drug-resistant strains of Mycobacterium tuberculosis is a major public health problem worldwide, and the identification of new efficient treatments is urgently needed. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterial growth. Using a rational approach, which includes molecular modelling studies, three series of azole pyrazole derivatives were designed through two synthetic pathways. The synthesized compounds were biologically evaluated for their inhibitory activity towards M. tuberculosis and their protein binding affinity (K D). Series 3 biarylpyrazole imidazole derivatives were the most effective with the isobutyl (10 f) and tert-butyl (10 g) compounds displaying optimal activity (MIC 1.562 mug/mL, K D 0.22 muM (10 f) and 4.81 muM (10 g)). The spectroscopic data showed that all the synthesised compounds produced a type II red shift of the heme Soret band indicating either direct binding to heme iron or (where less extensive Soret shifts are observed) putative indirect binding via an interstitial water molecule. Evaluation of biological and physicochemical properties identified the following as requirements for activity: LogP >4, H-bond acceptors/H-bond donors 4/0, number of rotatable bonds 5-6, molecular volume >340 A(3), topological polar surface area <40 A(2).
		+
		+	Design and Synthesis of Imidazole and Triazole Pyrazoles as Mycobacterium Tuberculosis CYP121A1 Inhibitors.,Kishk SM, McLean KJ, Sood S, Smith D, Evans JWD, Helal MA, Gomaa MS, Salama I, Mostafa SM, de Carvalho LPS, Levy CW, Munro AW, Simons C ChemistryOpen. 2019 Jul 23;8(7):995-1011. doi: 10.1002/open.201900227., eCollection 2019 Jul. PMID:31367508<ref>PMID:31367508</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 6geq" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Mycocyclosin synthase]]		[[Category: Mycocyclosin synthase]]
		+	[[Category: Mycto]]
	[[Category: Levy, C W]]		[[Category: Levy, C W]]
	[[Category: Antibiotic]]		[[Category: Antibiotic]]
	[[Category: Inhibitor complex p450]]		[[Category: Inhibitor complex p450]]
	[[Category: Oxidoreductase]]		[[Category: Oxidoreductase]]

OCA at 05:48, 7 August 2019

OCA — Wed, 07 Aug 2019 05:48:00 GMT

←Older revision		Revision as of 05:48, 7 August 2019
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-	'''Unreleased structure'''

-	~~The entry 6geq is ON HOLD until Paper Publication~~	+	==Crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP121A1 in complex with Triazole Pyrazole inhibitor 14a==
-		+	<StructureSection load='6geq' size='340' side='right'caption='[[6geq]], [[Resolution\|resolution]] 1.60Å' scene=''>
-	~~Authors: Levy, C.W.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[6geq]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GEQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GEQ FirstGlance]. <br>
-	~~Description:~~ Crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP121A1 in complex with Triazole Pyrazole inhibitor 14a	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EW5:1-phenyl-3-pyridin-4-yl-~{N}-(pyridin-4-ylmethyl)pyrazole-4-carboxamide'>EW5</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[Category: ~~Unreleased~~ Structures]]	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mycocyclosin_synthase Mycocyclosin synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.21.9 1.14.21.9] </span></td></tr>
-	[[Category: Levy, C.W]]	+	<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=6geq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6geq OCA], [http://pdbe.org/6geq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6geq RCSB], [http://www.ebi.ac.uk/pdbsum/6geq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6geq ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/CP121_MYCTO CP121_MYCTO]] Catalyzes C-C bond formation between the carbons ortho to the phenolic hydroxyl of cyclo(L-tyr-L-tyr) (cYY) producing mycocyclosin. Can also use cyclo(L-Tyr-L-Phe) (cYF), cyclo(L-Tyr-L-Trp) (cYW) and cyclo(L-Tyr-L-3,4-dihydroxyphenylalanine) (cY-DOPA) as substrate (By similarity).
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Mycocyclosin synthase]]
		+	[[Category: Levy, C W]]
		+	[[Category: Antibiotic]]
		+	[[Category: Inhibitor complex p450]]
		+	[[Category: Oxidoreductase]]

OCA at 05:16, 10 April 2019

OCA — Wed, 10 Apr 2019 05:16:19 GMT

←Older revision		Revision as of 05:16, 10 April 2019
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6geq is ON HOLD	+	The entry 6geq is ON HOLD until Paper Publication

	Authors: Levy, C.W.		Authors: Levy, C.W.

OCA: Protected "6geq" [edit=sysop:move=sysop]

OCA — Wed, 09 May 2018 05:03:48 GMT

Protected "6geq" [edit=sysop:move=sysop]

←Older revision

Revision as of 05:03, 9 May 2018

OCA: New page: '''Unreleased structure''' The entry 6geq is ON HOLD Authors: Levy, C.W. Description: Crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP121A1 in complex with Triazole ...

OCA — Wed, 09 May 2018 05:03:47 GMT

New page: '''Unreleased structure''' The entry 6geq is ON HOLD Authors: Levy, C.W. Description: Crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP121A1 in complex with Triazole ...

New page

'''Unreleased structure'''

The entry 6geq is ON HOLD

Authors: Levy, C.W.

Description: Crystal structure of Mycobacterium tuberculosis cytochrome P450 CYP121A1 in complex with Triazole Pyrazole inhibitor 14a
[[Category: Unreleased Structures]]
[[Category: Levy, C.W]]