1976
DOI: 10.1073/pnas.73.6.1848
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Amino acid sequence at the FdUMP binding site of thymidylate synthetase.

Abstract: Cyanogen bromide treatment of thymidylate synthetase of Lactobacillus casei, which had been converted to a ternary complex with [2-4CJFdUMP and 5,10-methylenetetrahydrofolate followed by Scarboxymethylation, yielded at least our visible peptide bands, the largest with a molecular weight of about 13,000, on polyacrylamide gel electrophoresis in sodium dodecyl sulfate-urea. Identical results were obtained with enzyme that had all four of its cysteinyl residues S-carboxymethylated with iodo [1-14C] (3,5,6) sugge… Show more

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Cited by 42 publications
(19 citation statements)
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“…The human enzyme has considerably more residues of cysteine, glycine, and arginine and fewer of histidine than the bacterial enzyme. The 2.5-fold more cysteine residues in the human enzyme are especially interesting because a cysteine residue is catalytically active (13,31,32) and binds FdUMP (28,33) We hope that the facile purification of high-activity human thymidylate synthetase described in this report will stimulate further investigations into the mechanisms of action and inhibition of this important enzyme from human sources.…”
Section: Discussionmentioning
confidence: 99%
“…The human enzyme has considerably more residues of cysteine, glycine, and arginine and fewer of histidine than the bacterial enzyme. The 2.5-fold more cysteine residues in the human enzyme are especially interesting because a cysteine residue is catalytically active (13,31,32) and binds FdUMP (28,33) We hope that the facile purification of high-activity human thymidylate synthetase described in this report will stimulate further investigations into the mechanisms of action and inhibition of this important enzyme from human sources.…”
Section: Discussionmentioning
confidence: 99%
“…In the course of this reaction a methylene group and hydride ion are contributed by CH2hPteGlu to the 5-position of dUMP, the latter being activated by a nucleophilic attack at the 6-position of dUMP (Pogolotti & Santi, 1977). The nucleophile was shown subsequently to be a specific cysteinyl residue of the enzyme (Bellisario et al, 1976;Pogolotti et al, 1976) and verified more recently by X-ray crystallographic studies on the 0006-2960/95/0434-1469$09.00/0 0 1995 American Chemical Society liganded structure of Escherichia coli TS (Matthews et al, 1990a,b;Montfort et al, 1990).…”
mentioning
confidence: 94%
“…The Cys at amino acid 490 (Fig. 3) is the probable binding site for FdUMP and dUMP (27,37,42,44) and has been proposed as the essential nucleophilic catalyst The alignments used to calculate shared amino acids are shown in Fig. 3.…”
Section: Oligonucleotides a 29-base Oligonucleotide Mixture 5' D[gg(mentioning
confidence: 99%