Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	X-ray and cryo-EM structures of inhibitor-bound cytochrome complexes for structure-based drug discovery.
Journal, issue, pages	IUCrJ, Vol. 5, Issue Pt 2, Page 200-210, Year 2018
Publish date	Mar 1, 2018
Authors	Kangsa Amporndanai / Rachel M Johnson / Paul M O'Neill / Colin W G Fishwick / Alexander H Jamson / Shaun Rawson / Stephen P Muench / S Samar Hasnain / Svetlana V Antonyuk /
PubMed Abstract	Cytochrome , a dimeric multi-subunit electron-transport protein embedded in the inner mitochondrial membrane, is a major drug target for the treatment and prevention of malaria and toxoplasmosis. ...Cytochrome , a dimeric multi-subunit electron-transport protein embedded in the inner mitochondrial membrane, is a major drug target for the treatment and prevention of malaria and toxoplasmosis. Structural studies of cytochrome from mammalian homologues co-crystallized with lead compounds have underpinned structure-based drug design to develop compounds with higher potency and selectivity. However, owing to the limited amount of cytochrome that may be available from parasites, all efforts have been focused on homologous cytochrome complexes from mammalian species, which has resulted in the failure of some drug candidates owing to toxicity in the host. Crystallographic studies of the native parasite proteins are not feasible owing to limited availability of the proteins. Here, it is demonstrated that cytochrome is highly amenable to single-particle cryo-EM (which uses significantly less protein) by solving the apo and two inhibitor-bound structures to ∼4.1 Å resolution, revealing clear inhibitor density at the binding site. Therefore, cryo-EM is proposed as a viable alternative method for structure-based drug discovery using both host and parasite enzymes.
External links	IUCrJ / PubMed:29765610 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	3.1 - 4.4 Å
Structure data	4286 6fo0 EMDB-4286, PDB-6fo0: CryoEM structure of bovine cytochrome bc1 in complex with the anti-malarial compound GSK932121 Method: EM (single particle) / Resolution: 4.1 Å 4288 6fo2 EMDB-4288, PDB-6fo2: CryoEM structure of bovine cytochrome bc1 with no ligand bound Method: EM (single particle) / Resolution: 4.4 Å 4292 6fo6 EMDB-4292, PDB-6fo6: CryoEM structure of bovine cytochrome bc1 in complex with the anti-malarial inhibitor SCR0911 Method: EM (single particle) / Resolution: 4.1 Å PDB-5okd: Crystal structure of bovine Cytochrome bc1 in complex with inhibitor SCR0911. Method: X-RAY DIFFRACTION / Resolution: 3.1 Å
Chemicals	ChemComp-PG4: TETRAETHYLENE GLYCOL / precipitantYM / Polyethylene glycol ChemComp-6PE: 1,2-DIHEXANOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE ChemComp-CDL: CARDIOLIPIN / phospholipidYM / Cardiolipin ChemComp-HEM: PROTOPORPHYRIN IX CONTAINING FE / Heme B ChemComp-9XE: 7-methoxy-3-methyl-2-[5-[4-(trifluoromethyloxy)phenyl]pyridin-3-yl]-1~{H}-quinolin-4-one ChemComp-LMT: DODECYL-BETA-D-MALTOSIDE / detergentYM ChemComp-PEE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine / DOPE, phospholipidYM / Discrete optimized protein energy ChemComp-HEC: HEME C / Heme C ChemComp-PO4: PHOSPHATE ION / Phosphate ChemComp-FES: FE2/S2 (INORGANIC) CLUSTER / Iron–sulfur cluster ChemComp-PX4: 1,2-DIMYRISTOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / DMPC, phospholipidYM / Dimyristoylphosphatidylcholine ChemComp-HOH: WATER / Water ChemComp-G8U: 3-chloro-6-(hydroxymethyl)-2-methyl-5-{4-[3-(trifluoromethoxy)phenoxy]phenyl}pyridin-4-ol ChemComp-DY2*: 7-methoxy-3-methyl-2-[5-[4-(trifluoromethyloxy)phenyl]pyridin-3-yl]quinolin-4-ol
Source	bos taurus (cattle) Bovine (cattle)
Keywords	ELECTRON TRANSPORT / antimalarial inhibitor / Qi site binder / MEMBRANE PROTEIN / Cryo-EM / Inhibitor binding / cytochrome bc1