7y5c: Difference between revisions
New page: '''Unreleased structure''' The entry 7y5c is ON HOLD Authors: Saw, W.-G., Wong, C.F., Grueber, G. Description: Cryo-EM structure of F-ATP synthase from Mycolicibacterium smegmatis (rot... |
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The | ==Cryo-EM structure of F-ATP synthase from Mycolicibacterium smegmatis (rotational state 2)== | ||
<StructureSection load='7y5c' size='340' side='right'caption='[[7y5c]], [[Resolution|resolution]] 4.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7y5c]] is a 20 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis Mycolicibacterium smegmatis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Y5C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y5C 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]] 4.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7y5c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y5c OCA], [https://pdbe.org/7y5c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y5c RCSB], [https://www.ebi.ac.uk/pdbsum/7y5c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y5c ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ATPB_MYCS2 ATPB_MYCS2] Produces ATP from ADP in the presence of a proton gradient across the membrane. The catalytic sites are hosted primarily by the beta subunits.[HAMAP-Rule:MF_01347] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The F(1)F(O)-ATP synthase is required for the viability of tuberculosis (TB) and nontuberculous mycobacteria (NTM) and has been validated as a drug target. Here, we present the cryo-EM structures of the Mycobacterium smegmatis F(1)-ATPase and the F(1)F(O)-ATP synthase with different nucleotide occupation within the catalytic sites and visualize critical elements for latent ATP hydrolysis and efficient ATP synthesis. Mutational studies reveal that the extended C-terminal domain (alphaCTD) of subunit alpha is the main element for the self-inhibition mechanism of ATP hydrolysis for TB and NTM bacteria. Rotational studies indicate that the transition between the inhibition state by the alphaCTD and the active state is a rapid process. We demonstrate that the unique mycobacterial gamma-loop and subunit delta are critical elements required for ATP formation. The data underline that these mycobacterium-specific elements of alpha, gamma, and delta are attractive targets, providing a platform for the discovery of species-specific inhibitors. | |||
Structural Elements Involved in ATP Hydrolysis Inhibition and ATP Synthesis of Tuberculosis and Nontuberculous Mycobacterial F-ATP Synthase Decipher New Targets for Inhibitors.,Wong CF, Saw WG, Basak S, Sano M, Ueno H, Kerk HW, Litty D, Ragunathan P, Dick T, Muller V, Noji H, Gruber G Antimicrob Agents Chemother. 2022 Dec 20;66(12):e0105622. doi: , 10.1128/aac.01056-22. Epub 2022 Nov 29. PMID:36445139<ref>PMID:36445139</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7y5c" style="background-color:#fffaf0;"></div> | ||
[[Category: Saw | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycolicibacterium smegmatis]] | |||
[[Category: Grueber G]] | |||
[[Category: Saw W-G]] | |||
[[Category: Wong CF]] | |||
Latest revision as of 10:31, 3 July 2024
Cryo-EM structure of F-ATP synthase from Mycolicibacterium smegmatis (rotational state 2)Cryo-EM structure of F-ATP synthase from Mycolicibacterium smegmatis (rotational state 2)
Structural highlights
FunctionATPB_MYCS2 Produces ATP from ADP in the presence of a proton gradient across the membrane. The catalytic sites are hosted primarily by the beta subunits.[HAMAP-Rule:MF_01347] Publication Abstract from PubMedThe F(1)F(O)-ATP synthase is required for the viability of tuberculosis (TB) and nontuberculous mycobacteria (NTM) and has been validated as a drug target. Here, we present the cryo-EM structures of the Mycobacterium smegmatis F(1)-ATPase and the F(1)F(O)-ATP synthase with different nucleotide occupation within the catalytic sites and visualize critical elements for latent ATP hydrolysis and efficient ATP synthesis. Mutational studies reveal that the extended C-terminal domain (alphaCTD) of subunit alpha is the main element for the self-inhibition mechanism of ATP hydrolysis for TB and NTM bacteria. Rotational studies indicate that the transition between the inhibition state by the alphaCTD and the active state is a rapid process. We demonstrate that the unique mycobacterial gamma-loop and subunit delta are critical elements required for ATP formation. The data underline that these mycobacterium-specific elements of alpha, gamma, and delta are attractive targets, providing a platform for the discovery of species-specific inhibitors. Structural Elements Involved in ATP Hydrolysis Inhibition and ATP Synthesis of Tuberculosis and Nontuberculous Mycobacterial F-ATP Synthase Decipher New Targets for Inhibitors.,Wong CF, Saw WG, Basak S, Sano M, Ueno H, Kerk HW, Litty D, Ragunathan P, Dick T, Muller V, Noji H, Gruber G Antimicrob Agents Chemother. 2022 Dec 20;66(12):e0105622. doi: , 10.1128/aac.01056-22. Epub 2022 Nov 29. PMID:36445139[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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