An unprecedented twist to ODCase catalytic activity.
Orotidine-5'-monophosphate decarboxylase (ODCase) has evolved to catalyze a decarboxylation reaction, most probably via a carbanion species at the C6 position of orotidine-5'-monophosphate. We reveal an unusual biochemical pathway of conversion of 6-cyano-uridine-5'-monophosphate by ODCase to barbiturate-5'-monophosphate via perhaps an electrophilic center at the C6 position, leading to inhibition. This potential of ODCase is very useful in the design of novel inhibitors.
Fujihashi
Masahiro
M
Molecular Design and Information Technology Center, Leslie Dan Faculty of Pharmacy, Toronto, ON M5S 2S2 Canada.
Bello
Angelica M
AM
Poduch
Ewa
E
Wei
Lianhu
L
Annedi
Subhash C
SC
Pai
Emil F
EF
Kotra
Lakshmi P
LP
D002384:Catalysis; D018360:Crystallography, X-Ray; D013058:Mass Spectrometry; D017014:Methanobacterium / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000737:chemistry* / Q000378:metabolism*; D055672:Static Electricity; D013997:Time Factors
D009955:Ornithine Decarboxylase