Abstract:
:Little is known about the catalytic mechanism of the recently discovered ThyX family of flavin-dependent thymidylate synthases that are required for thymidylate (deoxythymidine 5'-monophosphate) synthesis in a large number of microbial species. Using a combination of site-directed mutagenesis and biochemical measurements, we have identified several residues of the Helicobacter pylori ThyX protein with crucial roles in ThyX catalysis. By providing functional evidence that the active site(s) of homotetrameric ThyX proteins is formed by three different subunits, our findings suggest that ThyX proteins have evolved through multimerization of inactive monomers. Moreover, because the active-site configurations of ThyX proteins, present in many human pathogenic bacteria, and of human thymidylate synthase ThyA are different, our results will aid in the identification of compounds specifically inhibiting microbial growth.
journal_name
Proc Natl Acad Sci U S Aauthors
Leduc D,Graziani S,Lipowski G,Marchand C,Le Maréchal P,Liebl U,Myllykallio Hdoi
10.1073/pnas.0401365101keywords:
subject
Has Abstractpub_date
2004-05-11 00:00:00pages
7252-7issue
19eissn
0027-8424issn
1091-6490pii
0401365101journal_volume
101pub_type
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