Functional evidence for active site location of tetrameric thymidylate synthase X at the interphase of three monomers.
Proc Natl Acad Sci U S A
; 101(19): 7252-7, 2004 May 11.
Article
em En
| MEDLINE
| ID: mdl-15123820
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Timidilato Sintase
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
França