5nmi

From Proteopedia

(Difference between revisions)

Revision as of 13:08, 15 November 2023

Cytochrome bc1 bound to the inhibitor MJM170

Structural highlights

5nmi is a 22 chain structure with sequence from Bos taurus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.5Å
Ligands:	, , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.

Publication Abstract from PubMed

Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 muM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50, <30 nM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bc1 complex Qi site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites.

New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections.,McPhillie M, Zhou Y, El Bissati K, Dubey J, Lorenzi H, Capper M, Lukens AK, Hickman M, Muench S, Verma SK, Weber CR, Wheeler K, Gordon J, Sanders J, Moulton H, Wang K, Kim TK, He Y, Santos T, Woods S, Lee P, Donkin D, Kim E, Fraczek L, Lykins J, Esaa F, Alibana-Clouser F, Dovgin S, Weiss L, Brasseur G, Wirth D, Kent M, Hood L, Meunieur B, Roberts CW, Hasnain SS, Antonyuk SV, Fishwick C, McLeod R Sci Rep. 2016 Jul 14;6:29179. doi: 10.1038/srep29179. PMID:27412848^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ McPhillie M, Zhou Y, El Bissati K, Dubey J, Lorenzi H, Capper M, Lukens AK, Hickman M, Muench S, Verma SK, Weber CR, Wheeler K, Gordon J, Sanders J, Moulton H, Wang K, Kim TK, He Y, Santos T, Woods S, Lee P, Donkin D, Kim E, Fraczek L, Lykins J, Esaa F, Alibana-Clouser F, Dovgin S, Weiss L, Brasseur G, Wirth D, Kent M, Hood L, Meunieur B, Roberts CW, Hasnain SS, Antonyuk SV, Fishwick C, McLeod R. New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections. Sci Rep. 2016 Jul 14;6:29179. doi: 10.1038/srep29179. PMID:27412848 doi:http://dx.doi.org/10.1038/srep29179

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5nmi"

Categories: Bos taurus | Large Structures | Antonyuk SV | Capper NJ | Hasnain SS

@@ Line 3: / Line 3: @@
 <StructureSection load='5nmi' size='340' side='right'caption='[[5nmi]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5nmi]] is a 22 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=5NMI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5NMI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5nmi]] is a 22 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NMI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NMI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MJM:(4aS)-2-methyl-3-(4-phenoxyphenyl)-5,6,7,8-tetrahydroquinolin-4(4aH)-one'>MJM</scene>, <scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</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]] 3.5&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene>, <scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=HEC:HEME+C'>HEC</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MJM:(4aS)-2-methyl-3-(4-phenoxyphenyl)-5,6,7,8-tetrahydroquinolin-4(4aH)-one'>MJM</scene>, <scene name='pdbligand=PEE:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>PEE</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5nmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nmi OCA], [http://pdbe.org/5nmi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nmi RCSB], [http://www.ebi.ac.uk/pdbsum/5nmi PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nmi 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=5nmi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nmi OCA], [https://pdbe.org/5nmi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nmi RCSB], [https://www.ebi.ac.uk/pdbsum/5nmi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nmi 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/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. [[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/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.
+[https://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.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 25: @@
 [[Category: Bos taurus]]
 [[Category: Large Structures]]
-[[Category: Ubiquinol--cytochrome-c reductase]]
+[[Category: Antonyuk SV]]
-[[Category: Antonyuk, S V]]
+[[Category: Capper NJ]]
-[[Category: Capper, N J]]
+[[Category: Hasnain SS]]
-[[Category: Hasnain, S S]]
-[[Category: Inhibitor complex]]
-[[Category: Membrane protein]]

5nmi

From Proteopedia

Revision as of 13:08, 15 November 2023

Cytochrome bc1 bound to the inhibitor MJM170

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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