Functional evidence for active site location of tetrameric thymidylate synthase X at the interphase of three monomers - École polytechnique
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2004

Functional evidence for active site location of tetrameric thymidylate synthase X at the interphase of three monomers

Résumé

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.

Dates et versions

hal-00831844 , version 1 (10-06-2013)

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Citer

Damien Leduc, Sébastien Graziani, Gérard Lipowski, C. Marchand, P. Le Maréchal, et al.. Functional evidence for active site location of tetrameric thymidylate synthase X at the interphase of three monomers. Proceedings of the National Academy of Sciences of the United States of America, 2004, 101 (19), pp.7252-7257. ⟨10.1073/pnas.0401365101⟩. ⟨hal-00831844⟩
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