Flavoprotein structure and mechanism. 5. XXXX reductase and @entity16336 dehydrogenase as targets for a structure-based drug design.

@entity13745 @entity11922 @entity1527 @entity32241 @entity53577 @entity2041 @entity73286 @entity1110 @entity1526 @entity1432 @entity16336 @entity15942 @entity54660 @entity7247
@entity32241 reductase (TR) is a flavoenzyme that has been found only in parasitic protozoa of the order Kinetoplastida. The enzyme catalyzes the @entity1110 -dependent reduction of @entity53577 conjugates and is a key enzyme of the parasite's @entity1432 metabolism. Consequently, TR is an attractive target molecule for a structure-based drug development against @entity1526 , @entity7247 , and other diseases caused by trypanosomes and leishmanias. The three-dimensional structures of TR and of three enzyme substrate complexes have been solved. Several classes of compounds are discussed as guide structures for the design of specific inhibitors. Among them are tricyclic compounds such as @entity54660 and @entity11922 , which competitively inhibit TR but not the related host enzyme @entity2041 reductase, as well as oxidase activity-inducing @entity15942 and @entity73286 . @entity16336 dehydrogenase (LipDH) is another @entity13745 discussed as a target molecule for an antitrypanosomal therapy. In @entity1527 , an organism that is highly susceptible to oxidative stress, LipDH participates in the redox cycling of nifurtimox, one of the most effective anti-Chagas agents. In conclusion, the structurally related enzymes TR and LipDH exhibit an unusually high one-electron-reducing capacity. Consequently, turncoat inhibitors and other compounds inducing an oxidase activity in both enzymes are promising drug candidates against @entity1526 .
