Subnanomolar inhibitor of cytochrome bc1 complex designed by optimizing interaction with conformationally flexible residues.

ABSTRACT: Cytochrome bc(1) complex (EC 1.10.2.2, bc(1)), an essential component of the cellular respiratory chain and the photosynthetic apparatus in photosynthetic bacteria, has been identified as a promising target for new drugs and agricultural fungicides. X-ray diffraction structures of the free bc(1) complex and its complexes with various inhibitors revealed that the phenyl group of Phe274 in the binding pocket exhibited significant conformational flexibility upon different inhibitors binding to optimize respective pi-pi interactions, whereas the side chains of other hydrophobic residues showed conformational stability. Therefore, in the present study, a strategy of optimizing the pi-pi interaction with conformationally flexible residues was proposed to design and discover new bc(1) inhibitors

SUBMITTER: Zhao PL 

PROVIDER: S-EPMC2810320 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature