Inhibition of methylcoenzyme M methylreductase by a uridine 5'-diphospho-N-acetylglucosamine derivative.

Uridine-5'-diphospho-N-acetylglucosamine, when oxidized with periodate to the corresponding aldehyde (o-UDP-GlcNAc), was a potent inhibitor of the methylcoenzyme M methylreductase reaction which catalyzes the reductive demethylation of methylcoenzyme M to methane. The oxidation product, o-UDP-GlcNAc, appears to bind to the UDP-GlcNAc site of the enzyme and inhibits the reduction of methylcoenzyme M both by MRF or its active hydrolytic fragment HS-HTP. The kinetic patterns indicate that o-UDP-GlcNAc inhibition is noncompetitive with HS-HTP or MRF, and the Hill coefficient indicated that there was cooperativity between the UDP and HS-HTP binding sites. The methylreductase enzyme was protected from o-UDP-GlcNAc inhibition by prior exposure to low concentrations of MRF. HS-HTP, at the same concentration as MRF, was not effective in protecting the enzyme from inhibition by o-UDP-GlcNAc.