ATP synthases: bioinformatic based insights into how their electrochemically driven motor comprised of subunits a and c might serve as a drug target.
ATP synthases, widely distributed in bacteria, eukaryotic mitochondria and chloroplasts, are highly conserved multi-subunit complexes. Although the conserved acidic residue in the transmembrane helix of the c subunit functions in H+ transport, the surrounding residues differ among species. Such divergence could lead to different regulatory modes since pH-dependent H+ transport has been demonstrated in E. coli with a c subunit carrying an additional acidic residue in the helix. There is further divergence in the number of c subunits that form the ring structure which is determined by the higher ordered structure. Recently, it was suggested that certain chemicals recognize the a and c subunits of pathogenic bacterial F0. Since there may be structural divergence even in well-conserved ATP synthases, the c subunit-ring as well as the a subunit in F0 could be targets for drugs for specific bacterial species.
Maeda
Masatomo
M
Department of Molecular Biology, School of Pharmaceutical Sciences, Iwate Medical University, Shiwa, Iwate, 028-3694, Japan. mmaeda@iwate-med.ac.jp
D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D016503:Drug Delivery Systems / Q000379:methods*; D004563:Electrochemistry / Q000379:methods*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry*; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry*; D008956:Models, Chemical; D020409:Molecular Motor Proteins / Q000737:chemistry*; D011485:Protein Binding; D021122:Protein Subunits
D004791:Enzyme Inhibitors; D020409:Molecular Motor Proteins; D021122:Protein Subunits; D025261:Mitochondrial Proton-Translocating ATPases