ALKYLATION OF AN ACTIVE-SITE CYSTEINYL RESIDUE DURING SUBSTRATE-DEPENDENT INACTIVATION OF ESCHERICHIA-COLI S-ADENOSYLMETHIONINE DECARBOXYLASE

被引:21
作者
DIAZ, E [1 ]
ANTON, DL [1 ]
机构
[1] DUPONT CO,EXPTL STN,DEPT CENT RES & DEV,POB 80328,WILMINGTON,DE 19880
关键词
D O I
10.1021/bi00230a037
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
S-Adenosylmethionine decarboxylase from Escherichia coli is a member of a small class of enzymes' that uses a pyruvoyl prosthetic group. The pyruvoyl group is proposed to form a Schiff base with the substrate and then act as an electron sink facilitating decarboxylation. We have previously shown that once every 6000-7000 turnovers the enzyme undergoes an inactivation that results in a transaminated pyruvoyl group and the formation of an acrolein-like species from the methionine moiety. The acrolein then covalently alkylates the enzyme [Anton, D. L., & Kutny, R. (1987) Biochemistry 26, 6444]. After reduction of the alkylated enzyme with NaBH4, a tryptic peptide with the sequence Ala-Asp-Ile-Glu-Val-Ser-Thr-[S-(3-hydroxypropyl)Cys]-Gly-Val-Ile-Ser-Pro-Leu-Lys was isolated. This corresponds to acrolein alkylation of a cysteine residue in the second tryptic peptide from the NH2 terminal of the alpha-subunit [Anton, D. L., & Kutny, R. (1987) J. Biol. Chem. 262, 2817-2822]. The modified residue derived is from Cys-140 of the proenzyme [Tabor, C. W., & Tabor, H. (1987) J. Biol. Chem. 262, 16037-16040] and lies in the only sequence conserved between rat liver and E. coli S-adenosylmethionine decarboxylase [Pajunen et al. (1988) J. Biol. Chem. 263, 17040-17049]. We suggest that the alkylated Cys residue could have a role in the catalytic mechanism.
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页码:4078 / 4081
页数:4
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