Structure of Ralstonia eutropha Flavohemoglobin in Complex with Three Antibiotic Azole Compounds.

摘要: Flavohemoglobins (flavoHbs) are enzymes that operate primarily as nitric oxide dioxygenases and shuttle thereby electrons among NAD(P)H, FAD, heme, a ligated redox-active substrate such O2. They function in the bacterial defense against nitrosative stress therefore considered targets for new antibiotic drugs. Recently, azole derivatives were proven to be attractive dioxygenase inhibitors, explore their binding characteristics, we determined X-ray structure of flavoHb from Ralstonia eutropha complex with miconazole (FHPM), econazole (FHPE), ketoconazole (FHPK). In agreement UV−vis spectroscopic data, one compound binds inside distal heme pocket ligates iron by its imidazole substituent. The two additional substituents, mostly chlorinated phenyl groups, form series van der Waals contacts protein matrix. Both interactions explain high affinity flavoHbs, constants being 2.6, 1.2, 11.6 ...