Open AccessStructure of the Y94F mutant of Escherichia coli thymidylate synthase
Author(s) -
Hyatt David C.,
Honts Jerry E.,
Maley Gladys F.,
Maley Frank,
Roberts Sue A.,
Changchien Liming,
Montfort William R.
Publication year - 2006
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309106029691
Subject(s) - thymidylate synthase , mutant , escherichia coli , chemistry , stereochemistry , ternary complex , biochemistry , enzyme , biology , genetics , fluorouracil , chemotherapy , gene
Tyr94 of Escherichia coli thymidylate synthase is thought to be involved, either directly or by activation of a water molecule, in the abstraction of a proton from C5 of the 2′‐deoxyuridine 5′‐monophosphate (dUMP) substrate. Mutation of Tyr94 leads to a 400‐fold loss in catalytic activity. The structure of the Y94F mutant has been determined in the native state and as a ternary complex with thymidine 5′‐monophosphate (dTMP) and 10‐propargyl 5,8‐dideazafolate (PDDF). There are no structural changes ascribable to the mutation other than loss of a water molecule hydrogen bonded to the tyrosine OH, which is consistent with a catalytic role for the phenolic OH.