A member of a new class of GTP cyclohydrolases produces formylaminopyrimidine nucleotide monophosphates

被引:30
作者
Graham, DE [1 ]
Xu, HM [1 ]
White, RH [1 ]
机构
[1] Virginia Polytech Inst & State Univ, Dept Biochem, Blacksburg, VA 24061 USA
关键词
D O I
10.1021/bi0268798
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The hyperthermophilic euryarchaeon Methanococcus jannaschii has no recognizable homologues of the canonical GTP cyclohydrolase enzymes that are required for riboflavin and pteridine biosyntheses. Instead, it uses a new type of thermostable GTP cyclohydrolase enzyme that produces 2-amino-5-formylamino-6-ribofuranosylamino-4(3H)-pyrimidinone ribonucleotide monophosphate and inorganic phosphate. Whereas canonical GTP cyclohydrolases produce this formylamino-pyrimidine nucleotide as a reaction intermediate, this compound is shown to be an end product of the purified recombinant M. jannaschii enzyme. Unlike other enzymes that hydrolyze the alpha-beta phosphate anhydride bond of GTP, this new enzyme completely hydrolyzes pyrophosphate to inorganic phosphate. As a result, the enzyme has a steady-state turnover of 21 min(-1) which is much faster than those of canonical GTP cyclohydrolase enzymes. The effects of substrate analogues and inhibitors suggest that the GTP cyclohydrolase and pyrophosphate phosphohydrolase activities occur at independent sites, although both activities depend on Mg2+.
引用
收藏
页码:15074 / 15084
页数:11
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