Structure of a human carcinogen-converting enzyme, SULT1A1. Structural and kinetic implications of substrate inhibition.

摘要: Sulfonation catalyzed by sulfotransferase enzymes plays an important role in chemical defense mechanisms against various xenobiotics but also bioactivates carcinogens. A major human sulfotransferase, SULT1A1, metabolizes and/or many endogenous compounds and is implicated a range of cancers because its ability to modify diverse promutagen procarcinogen xenobiotics. The crystal structure SULT1A1 reported here the first complexed with xenobiotic substrate. An unexpected finding that enzyme accommodates not one two molecules model substrate p-nitrophenol active site. This result supported kinetic data for show inhibition this small xenobiotic. extended site consistent binding diiodothyronine cannot easily accommodate β-estradiol, although both are known substrates. observation, together evidence disorder-order transition suggests flexible can adapt architecture accept hydrophobic substrates varying sizes, shapes flexibility. Thus provides molecular basis reveals clues as how sulfonates wide variety lipophilic compounds.