7y5d: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7y5d]] 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=7Y5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y5D FirstGlance]. <br> | <table><tr><td colspan='2'>[[7y5d]] 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=7Y5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Y5D FirstGlance]. <br> | ||
</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=7y5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y5d OCA], [https://pdbe.org/7y5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y5d RCSB], [https://www.ebi.ac.uk/pdbsum/7y5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y5d ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 7.3Å</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=7y5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7y5d OCA], [https://pdbe.org/7y5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7y5d RCSB], [https://www.ebi.ac.uk/pdbsum/7y5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7y5d ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ | [https://www.uniprot.org/uniprot/ATPA_MYCS2 ATPA_MYCS2] Produces ATP from ADP in the presence of a proton gradient across the membrane. The alpha chain is a regulatory subunit.[HAMAP-Rule:MF_01346] | ||
<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> | |||
</div> | |||
<div class="pdbe-citations 7y5d" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 10:31, 3 July 2024
Cryo-EM structure of F-ATP synthase from Mycolicibacterium smegmatis (rotational state 3) (backbone)Cryo-EM structure of F-ATP synthase from Mycolicibacterium smegmatis (rotational state 3) (backbone)
Structural highlights
FunctionATPA_MYCS2 Produces ATP from ADP in the presence of a proton gradient across the membrane. The alpha chain is a regulatory subunit.[HAMAP-Rule:MF_01346] 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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