Shifting the metallocentric molybdoenzyme paradigm: the importance of pyranopterin coordination

摘要: In this review, we test the hypothesis that pyranopterin coordination plays a critical role in defining substrate reactivities four families of mononuclear molybdenum and tungsten enzymes (Mo/W-enzymes). Enzyme containing single dithiolene chelate have been demonstrated to reactivity towards two (sulfite oxidase, SUOX-fold) five (xanthine dehydrogenase, XDH-fold) types substrate, whereas major family bis-pyranopterin (dimethylsulfoxide reductase, DMSOR-fold) is reactive eight substrate. A second enzyme (aldehyde oxidoreductase, AOR-fold) catalyzes type reaction. The diversity reactions catalyzed by each correlates with active site variability, also number pyranopterins their protein. case AOR-fold enzymes, inflexibility limited specificity (oxidation aldehydes). examples SUOX-fold DMSOR-fold observe three histidine-containing charge-transfer relays can: (1) connect piperazine ring substrate-binding (SUOX-fold enzymes); (2) provide inter-pyranopterin communication (DMSOR-fold (3) pyran oxygen deeply buried water molecules (the NarGHI-type nitrate reductases). Finally, sequence data mining reveals bacterial species whose predicted proteomes contain large numbers (up 64) Mo/W-enzymes, being dominant. These analyses reveal an inverse correlation between Mo/W-enzyme content pathogenicity.