title: ATP synthase: a molecular therapeutic drug target for antimicrobial and antitumor peptides.
abstract: In this review we discuss the role of ATP synthase as a molecular drug target for natural and synthetic antimicrobial/ antitumor peptides. We start with an introduction of the universal nature of the ATP synthase enzyme and its role as a biological nanomotor. Significant structural features required for catalytic activity and motor functions of ATP synthase are described. Relevant details regarding the presence of ATP synthase on the surface of several animal cell types, where it is associated with multiple cellular processes making it a potential drug target with respect to antimicrobial peptides and other inhibitors such as dietary polyphenols, is also reviewed. ATP synthase is known to have about twelve discrete inhibitor binding sites including peptides and other inhibitors located at the interface of α/β subunits on the F(1) sector of the enzyme. Molecular interaction of peptides at the β DEELSEED site on ATP synthase is discussed with specific examples. An inhibitory effect of other natural/synthetic inhibitors on ATP is highlighted to explore the therapeutic roles played by peptides and other inhibitors. Lastly, the effect of peptides on the inhibition of the Escherichia coli model system through their action on ATP synthase is presented.
authors: Department of Biological & Environmental Sciences, Alabama A&M University, Normal, AL 35762, USA. Zulfiqar.ahmad@aamu.edu
authors: Zulfiqar
authors: Z
authors: Ahmad
authors: Florence
authors: F
authors: Okafor
authors: Sofiya
authors: S
authors: Azim
authors: Thomas F
authors: TF
authors: Laughlin
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D005658:Fungi / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D058990:Molecular Targeted Therapy; D009181:Mycoses / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D014777:Virus Diseases / Q000188:drug therapy; D014780:Viruses / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010455:Peptides; D000251:Adenosine Triphosphatases