OCA at 12:09, 16 January 2019

2019-01-16T12:09:15Z

← Older revision		Revision as of 12:09, 16 January 2019
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	~~'''Unreleased structure'''~~

	The ~~entry 6haw~~ is ~~ON HOLD~~		==Crystal structure of bovine cytochrome bc1 in complex with 2-pyrazolyl quinolone inhibitor WDH2G7==
			<StructureSection load='6haw' size='340' side='right' caption='[[6haw]], [[Resolution\|resolution]] 3.45Å' scene=''>
			== Structural highlights ==
			<table><tr><td colspan='2'>[[6haw]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HAW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HAW FirstGlance]. <br>
			</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6PE:1,2-DIHEXANOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>6PE</scene>, <scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=FX2:7-methoxy-3-methyl-2-[1-[[4-(trifluoromethyloxy)phenyl]methyl]pyrazol-4-yl]-3~{H}-quinolin-4-one'>FX2</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=LMT:DODECYL-BETA-D-MALTOSIDE'>LMT</scene>, <scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=PX4:1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PX4</scene>, <scene name='pdbligand=PX6:1,2-DIPALMITOYL-SN-GLYCERO-3-PHOSPHATE'>PX6</scene></td></tr>
			<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Ubiquinol--cytochrome-c_reductase Ubiquinol--cytochrome-c reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.10.2.2 1.10.2.2] </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=6haw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6haw OCA], [http://pdbe.org/6haw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6haw RCSB], [http://www.ebi.ac.uk/pdbsum/6haw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6haw ProSAT]</span></td></tr>
			</table>
			== Function ==
			[[http://www.uniprot.org/uniprot/QCR7_BOVIN QCR7_BOVIN]] This is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. This component is involved in redox-linked proton pumping. [[http://www.uniprot.org/uniprot/CYB_BOVIN CYB_BOVIN]] Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is a respiratory chain that generates an electrochemical potential coupled to ATP synthesis. [[http://www.uniprot.org/uniprot/QCR8_BOVIN QCR8_BOVIN]] This is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. This subunit, together with cytochrome b, binds to ubiquinone. [[http://www.uniprot.org/uniprot/UCRI_BOVIN UCRI_BOVIN]] Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is a respiratory chain that generates an electrochemical potential coupled to ATP synthesis. The transit peptide of the Rieske protein seems to form part of the bc1 complex and is considered to be the subunit 11/IX of that complex. [[http://www.uniprot.org/uniprot/QCR2_BOVIN QCR2_BOVIN]] This is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. The core protein 2 is required for the assembly of the complex. [[http://www.uniprot.org/uniprot/QCR6_BOVIN QCR6_BOVIN]] This is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. This protein may mediate formation of the complex between cytochromes c and c1. [[http://www.uniprot.org/uniprot/QCR1_BOVIN QCR1_BOVIN]] This is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. This protein may mediate formation of the complex between cytochromes c and c1. [[http://www.uniprot.org/uniprot/CY1_BOVIN CY1_BOVIN]] This is the heme-containing component of the cytochrome b-c1 complex, which accepts electrons from Rieske protein and transfers electrons to cytochrome c in the mitochondrial respiratory chain. [[http://www.uniprot.org/uniprot/QCR9_BOVIN QCR9_BOVIN]] This is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. This subunit interacts with cytochrome c1.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			A series of 2-pyrazolyl quinolones has been designed and synthesized in 5-7 steps to optimize for both in vitro antimalarial potency and various in vitro drug metabolism and pharmacokinetics (DMPK) features. The most potent compounds display no cross-resistance with multidrug resistant parasite strains (W2) compared to drug sensitive strains (3D7), with IC50 (concentration of drug required to achieve half maximal growth suppression) values in the range of 15-33 nM. Furthermore, members of the series retain moderate activity against the atovaquone-resistant parasite isolate (TM90C2B). The described 2-pyrazoyl series displays improved DMPK properties, including improved aqueous solubility compared to previously reported quinolone series and acceptable safety margin through in vitro cytotoxicity assessment. The 2-pyrazolyl quinolones are believed to bind to the ubiquinone-reducing Qi site of the parasite bc 1 complex, which is supported by crystallographic studies of bovine cytochrome bc 1 complex.

	~~Authors:~~ Amporndanai, K., ~~Hong~~, ~~W.D.~~, O'Neill~~, P~~.M., ~~Hasnain, S~~.S.~~, Antonyuk, S~~.V.		Potent Antimalarial 2-Pyrazolyl Quinolone bc 1 (Qi) Inhibitors with Improved Drug-like Properties.,David Hong W, Leung SC, Amporndanai K, Davies J, Priestley RS, Nixon GL, Berry NG, Samar Hasnain S, Antonyuk S, Ward SA, Biagini GA, O'Neill PM ACS Med Chem Lett. 2018 Oct 19;9(12):1205-1210. doi:, 10.1021/acsmedchemlett.8b00371. eCollection 2018 Dec 13. PMID:30613327<ref>PMID:30613327</ref>

	~~Description: Crystal structure~~ of ~~bovine cytochrome bc1 in complex with 2~~-~~pyrazolyl quinolone inhibitor WDH2G7~~		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[Category: Unreleased Structures]]~~		</div>
	~~[[Category: Hasnain, S.S]]~~		<div class="pdbe-citations 6haw" style="background-color:#fffaf0;"></div>
	[[Category: ~~O'Neill, P.M~~]]		== References ==
	[[Category: ~~Antonyuk, S.V~~]]		<references/>
			__TOC__
			</StructureSection>
			[[Category: Bos taurus]]
			[[Category: Ubiquinol--cytochrome-c reductase]]
	[[Category: Amporndanai, K]]		[[Category: Amporndanai, K]]
	[[Category: Hong, W.D]]		[[Category: Antonyuk, S V]]
			[[Category: Hasnain, S S]]
			[[Category: Hong, W D]]
			[[Category: Neill, P M.O]]
			[[Category: Cytochrome bc1]]
			[[Category: Electron transport]]
			[[Category: Malaria]]

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

2018-08-15T15:04:29Z

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

← Older revision	Revision as of 15:04, 15 August 2018
(No difference)

OCA: New page: '''Unreleased structure''' The entry 6haw is ON HOLD Authors: Amporndanai, K., Hong, W.D., O'Neill, P.M., Hasnain, S.S., Antonyuk, S.V. Description: Crystal structure of bovine cytochr...

2018-08-15T15:04:28Z

New page: '''Unreleased structure''' The entry 6haw is ON HOLD Authors: Amporndanai, K., Hong, W.D., O'Neill, P.M., Hasnain, S.S., Antonyuk, S.V. Description: Crystal structure of bovine cytochr...

New page

'''Unreleased structure'''

The entry 6haw is ON HOLD

Authors: Amporndanai, K., Hong, W.D., O'Neill, P.M., Hasnain, S.S., Antonyuk, S.V.

Description: Crystal structure of bovine cytochrome bc1 in complex with 2-pyrazolyl quinolone inhibitor WDH2G7
[[Category: Unreleased Structures]]
[[Category: Hasnain, S.S]]
[[Category: O'Neill, P.M]]
[[Category: Antonyuk, S.V]]
[[Category: Amporndanai, K]]
[[Category: Hong, W.D]]

6haw - Revision history

OCA at 12:09, 16 January 2019

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

OCA: New page: '''Unreleased structure''' The entry 6haw is ON HOLD Authors: Amporndanai, K., Hong, W.D., O'Neill, P.M., Hasnain, S.S., Antonyuk, S.V. Description: Crystal structure of bovine cytochr...