Inhibition of thymidylate synthase by pyridoxal phosphate.
1. Pyridoxal phosphate (PLP) reversibly inhibited thymidylate synthase from Lactobacillus casei with a KI of 0.6-0.9 microM. 2. The inhibition was competitive with dUMP and noncompetitive with 5,10-methylenetetrahydrofolate which is consistent with an ordered addition of substrates. 3. The spectrum of PLP was altered by the addition of thymidylate synthase. The spectral changes suggest formation of a thiohemiacetal with an enzyme sulfhydryl group rather than Schiff base formation with a lysine side chain.
Chen
S C
SC
Department of Chemistry, Auburn University, AL 36849.
Daron
H H
HH
Aull
J L
JL
D001667:Binding, Competitive; D003856:Deoxyuracil Nucleotides / Q000378:metabolism; D007780:Lacticaseibacillus casei / Q000201:enzymology*; D011732:Pyridoxal Phosphate / Q000494:pharmacology*; D013053:Spectrophotometry; D013763:Tetrahydrofolates / Q000378:metabolism; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*
D003856:Deoxyuracil Nucleotides; D013763:Tetrahydrofolates; C013123:5,10-methylenetetrahydrofolic acid; D011732:Pyridoxal Phosphate; C007267:2'-deoxyuridylic acid; D013940:Thymidylate Synthase