8e9h: Difference between revisions
New page: '''Unreleased structure''' The entry 8e9h is ON HOLD Authors: Liang, Y., Rubinstein, J.L. Description: Mycobacterial respiratory complex I, fully-inserted quinone [[Category: Unrelease... |
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The | ==Mycobacterial respiratory complex I, fully-inserted quinone== | ||
<StructureSection load='8e9h' size='340' side='right'caption='[[8e9h]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8e9h]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E9H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E9H FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=MQ9:MENAQUINONE-9'>MQ9</scene>, <scene name='pdbligand=XP2:(2R)-3-{[(R)-hydroxy({(1S,2R,3R,4R,5S,6S)-3,4,5-trihydroxy-2-(alpha-D-mannopyranosyloxy)-6-[(6-O-undecanoyl-beta-D-mannopyranosyl)oxy]cyclohexyl}oxy)phosphoryl]oxy}-2-(octanoyloxy)propyl+undecanoate'>XP2</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=8e9h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e9h OCA], [https://pdbe.org/8e9h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e9h RCSB], [https://www.ebi.ac.uk/pdbsum/8e9h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e9h ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0QU37_MYCS2 A0QU37_MYCS2] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Oxidative phosphorylation, the combined activity of the electron transport chain (ETC) and adenosine triphosphate synthase, has emerged as a valuable target for the treatment of infection by Mycobacterium tuberculosis and other mycobacteria. The mycobacterial ETC is highly branched with multiple dehydrogenases transferring electrons to a membrane-bound pool of menaquinone and multiple oxidases transferring electrons from the pool. The proton-pumping type I nicotinamide adenine dinucleotide (NADH) dehydrogenase (Complex I) is found in low abundance in the plasma membranes of mycobacteria in typical in vitro culture conditions and is often considered dispensable. We found that growth of Mycobacterium smegmatis in carbon-limited conditions greatly increased the abundance of Complex I and allowed isolation of a rotenone-sensitive preparation of the enzyme. Determination of the structure of the complex by cryoEM revealed the "orphan" two-component response regulator protein MSMEG_2064 as a subunit of the assembly. MSMEG_2064 in the complex occupies a site similar to the proposed redox-sensing subunit NDUFA9 in eukaryotic Complex I. An apparent purine nucleoside triphosphate within the NuoG subunit resembles the GTP-derived molybdenum cofactor in homologous formate dehydrogenase enzymes. The membrane region of the complex binds acyl phosphatidylinositol dimannoside, a characteristic three-tailed lipid from the mycobacterial membrane. The structure also shows menaquinone, which is preferentially used over ubiquinone by gram-positive bacteria, in two different positions along the quinone channel, comparable to ubiquinone in other structures and suggesting a conserved quinone binding mechanism. | |||
Structure of mycobacterial respiratory complex I.,Liang Y, Plourde A, Bueler SA, Liu J, Brzezinski P, Vahidi S, Rubinstein JL Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2214949120. doi: , 10.1073/pnas.2214949120. Epub 2023 Mar 23. PMID:36952383<ref>PMID:36952383</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8e9h" style="background-color:#fffaf0;"></div> | ||
[[Category: Liang | |||
==See Also== | |||
*[[Response regulator 3D structure|Response regulator 3D structure]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycolicibacterium smegmatis MC2 155]] | |||
[[Category: Liang Y]] | |||
[[Category: Rubinstein JL]] | |||
Latest revision as of 13:03, 25 December 2024
Mycobacterial respiratory complex I, fully-inserted quinoneMycobacterial respiratory complex I, fully-inserted quinone
Structural highlights
FunctionPublication Abstract from PubMedOxidative phosphorylation, the combined activity of the electron transport chain (ETC) and adenosine triphosphate synthase, has emerged as a valuable target for the treatment of infection by Mycobacterium tuberculosis and other mycobacteria. The mycobacterial ETC is highly branched with multiple dehydrogenases transferring electrons to a membrane-bound pool of menaquinone and multiple oxidases transferring electrons from the pool. The proton-pumping type I nicotinamide adenine dinucleotide (NADH) dehydrogenase (Complex I) is found in low abundance in the plasma membranes of mycobacteria in typical in vitro culture conditions and is often considered dispensable. We found that growth of Mycobacterium smegmatis in carbon-limited conditions greatly increased the abundance of Complex I and allowed isolation of a rotenone-sensitive preparation of the enzyme. Determination of the structure of the complex by cryoEM revealed the "orphan" two-component response regulator protein MSMEG_2064 as a subunit of the assembly. MSMEG_2064 in the complex occupies a site similar to the proposed redox-sensing subunit NDUFA9 in eukaryotic Complex I. An apparent purine nucleoside triphosphate within the NuoG subunit resembles the GTP-derived molybdenum cofactor in homologous formate dehydrogenase enzymes. The membrane region of the complex binds acyl phosphatidylinositol dimannoside, a characteristic three-tailed lipid from the mycobacterial membrane. The structure also shows menaquinone, which is preferentially used over ubiquinone by gram-positive bacteria, in two different positions along the quinone channel, comparable to ubiquinone in other structures and suggesting a conserved quinone binding mechanism. Structure of mycobacterial respiratory complex I.,Liang Y, Plourde A, Bueler SA, Liu J, Brzezinski P, Vahidi S, Rubinstein JL Proc Natl Acad Sci U S A. 2023 Mar 28;120(13):e2214949120. doi: , 10.1073/pnas.2214949120. Epub 2023 Mar 23. PMID:36952383[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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