Premium
Functions of three GTP cyclohydrolase II proteins of S. coelicolor
Author(s) -
Bandarian Vahe,
Spoonamore James E.,
Dahlgran Annie L.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb54-d
Subject(s) - biochemistry , gene , biology , genome , gtp cyclohydrolase i , computational biology , enzyme , cofactor , tetrahydrobiopterin
The genome of S. coelicolor contains three open reading frames with significant sequence identity (> 40 %) to GTP cyclohydrolase II, which initiates the biosynthesis of riboflavin by conversion of guanosine 5′‐triphosphate to 2,5‐diamino‐6‐hydroxy‐4‐(ribosylamino)pyrimidine 5′‐phosphate. The physiological significance of the redundancy in these proteins is not known; however, the gene contexts of the three proteins differ suggesting that they may serve alternate biological niches. Examination of the gene contexts and comparison to genomes of other organisms suggest a role for two of these clusters: one in the biosynthesis of riboflavin and the second in the production of toxoflavin or a related molecule. However, the function of the third cluster is not known. We have cloned, overexpressed, purified and characterized each of the proteins annotated as GCH II and show that in contrast to the annotation one of the proteins produces a formylamino analog of the canonical GCH II protein. Moreover, we show that a second protein in the cluster that bears this protein utilizes the product of this enzyme as a substrate. Our data are consistent with involvement of this cluster in production of a novel purine‐based metabolite the identity of which remains to be established. The research has been supported by a Career Award in Biomedical Sciences from the Burroughs Wellcome Fund and by the National Institutes of Health.