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7y5b

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Cryo-EM structure of F-ATP synthase from Mycolicibacterium smegmatis (rotational state 1)

Structural highlights

7y5b is a 20 chain structure with sequence from Mycolicibacterium smegmatis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 4.4Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0R205_MYCS2 F(1)F(0) ATP synthase produces ATP from ADP in the presence of a proton or sodium gradient. F-type ATPases consist of two structural domains, F(1) containing the extramembraneous catalytic core and F(0) containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation.[ARBA:ARBA00025198][HAMAP-Rule:MF_01396] Key component of the F(0) channel; it plays a direct role in translocation across the membrane. A homomeric c-ring of between 10-14 subunits forms the central stalk rotor element with the F(1) delta and epsilon subunits.[HAMAP-Rule:MF_01396]

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^[1]

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

References

↑ Wong CF, Saw WG, Basak S, Sano M, Ueno H, Kerk HW, Litty D, Ragunathan P, Dick T, Müller V, Noji H, Grüber G. Structural Elements Involved in ATP Hydrolysis Inhibition and ATP Synthesis of Tuberculosis and Nontuberculous Mycobacterial F-ATP Synthase Decipher New Targets for Inhibitors. Antimicrob Agents Chemother. 2022 Dec 20;66(12):e0105622. PMID:36445139 doi:10.1128/aac.01056-22