MetaCyc Enzyme: adenosylmethionine decarboxylase

Gene: speD Accession Numbers: EG10962 (MetaCyc), b0120, ECK0119

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of adenosylmethionine decarboxylase = [SpeD]4[SpeD]4
         α cleavage product of SpeD = SpeD
         β cleavage product of SpeD = SpeD

Adenosylmethionine decarboxylase is an important enzyme of polyamine biosynthesis in all domains of life. It has been extensively studied in microorganisms, plants and animals. It catalyzes the removal of the carboxylate group of S-adenosyl-L-methionine producing S-adenosyl-L-methioninamine. This compound then acts as the n-propylamine group donor for the synthesis of spermidine from putrescine by spermidine synthase. Spermidine is an important negative regulator of adenosylmethionine decarboxylase, affecting the entire polyamine biosynthesis pathway.

This enzyme belongs to a small class of decarboxylating enzymes that utilize covalently bound pyruvate (pyruvoyl group). Class 1 enzymes are found in bacteria and archaea, while Class 2 are found in eukaryotes. These two classes show almost no detectable sequence homology with each other and do not show similarity to other known pyruvoyl-dependent amino acid decarboxylases. Class 1A is enzymes are found primarily in Gram-negative bacteria, including E. coli while Class 1B are found in some Gram-positive bacteria and archaea. These two classes show only low levels of amino acid sequence similarity. A homology model of the core structure of the E. coli enzyme based on the crystal structures of the human (Class 2) and Thermotoga maritima (Class 1B) enzymes has been proposed [Toms04].

E. coli S- adenosylmethionine (AdoMet) decarboxylase, encoded by the speD gene, is a heterooctamer of four α and four β chains arranged as a tetramer of α/β heterodimers. It has 1 pyruvoyl residue for each αβ pair. The amino terminus of the larger α subunit has a pyruvoyl group while the smaller β subunit has a free amino terminus [Anton87]. The enzyme is first synthesized as a proenzyme of 30.4 kDa polypeptide, which then undergoes post-translational autocatalytic cleavage at the Lys111- Ser112 peptide bond to form the 18 kDa α and 12.4 kDa β subunits. The N-terminal serine residue of the α chain is converted to a pyruvoyl group by nonhydrolytic serinolysis [Tabor87] and summarized in [Toms04].

The pyruvoyl group acts analogously to pyridoxal phosphate cofactor by forming a Schiff base with the amino group of the substrate and then serving as an electron sink to facilitate the decarboxylation. AdoMet decarboxylase requires a metal cation such as Mg2+ for activity and is not activated by putrescine. Mn2+ binding studies shows a stoichiometry of one cation site per pyruvoyl group [Markham82].

AdoMet decarboxylase from E. coli undergoes substrate-dependent inactivation that involves two events: transamination of the nascent product and the pyruvoyl group, and alkylation of the enzyme with the carbons 2, 3 and 4 of the methionyl moiety of AdoMet. This may occur after the normal decarboxylation reaction by incorrect protonation of the enolate intermediate [Anton87a].

Cys-140 was shown to play a role in the catalytic mechanism [Diaz91]. Using recombinant E. coli enzyme expressed in E. coli BL21(DE3), mass spectrometry analysis showed that the enzyme can be inactivated in vivo by mechanism-based modification of the α subunit through alkylation of the Cys-140 sulfhydryl group. The alkylation was derived from decarboxylated AdoMet [Li01].

The E. coli enzyme was first purified from E. coli W [Wickner70].

Map Position: [134,788 <- 135,582]

Unification Links: ASAP:ABE-0000416 , CGSC:158 , EchoBASE:EB0955 , EcoGene:EG10962 , Entrez-gene:947719 , OU-Microarray:b0120 , PortEco:speD , RegulonDB:EG10962

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Molecular Function: GO:0004014 - adenosylmethionine decarboxylase activity Inferred from experiment [Markham82]

MultiFun Terms: metabolism central intermediary metabolism polyamine biosynthesis

Imported from EcoCyc 02-Jun-2015 by Paley S , SRI International

Enzymatic reaction of: adenosylmethionine decarboxylase

Synonyms: S-adenosylmethionine decarboxylase, ADOMETDC, S-adenosyl-L-methionine carboxy-lyase

EC Number:

S-adenosyl-L-methionine + H+ <=> CO2 + S-adenosyl 3-(methylthio)propylamine

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: superpathway of arginine and polyamine biosynthesis , superpathway of polyamine biosynthesis I , spermidine biosynthesis I

Imported from EcoCyc 02-Jun-2015 by Paley S , SRI International

The enzyme was activated by cations of varying charge and ionic radius. In addition to those listed here, the divalent ions of the lanthanides terbium, europium and gadolinium were also activators. Na+, K+, Cu2+ and Ni2+ were not activators and Zn2+ was a potent inhibitor [Lu07].

A number of nucleosides related to S-adenosylmethionine were tested as potential aminopropyltransferase inhibitors of both the E. coli and rat prostate adenosylmethionine decarboxylases. Differences were found between the bacterial and mammalian enzymes. The most potent inhibitor was 5'-(dimethylsulfonio)-5'-deoxyadenosine (dimethyl(5'-adenosyl)sulfonium) for both enzymes. 5'-amino-5'-deoxyadenosine showed only 2% inhibition of the E. coli enzyme at 1 mM [Pegg86].

Inhibition of adenosylmethionine decarboxylase by spermidine in E. coli [Kashiwagi88] appears to be the most significant regulator of polyamine biosynthesis, probably limiting it when the intracellular spermidine concentration becomes excessive (reviewed in [Tabor85] and in Charlier, D. and N. Glansdorff (2004) "Biosynthesis of Arginine and Polyamines." EcoSal [ECOSAL]).

Cofactors or Prosthetic Groups: pyruvate [Markham82, Tabor87], Mg2+ [Markham82]

Cofactor Binding Comment: requires Mg++ for activity [Weitkamp91]

Activators (Unknown Mechanism): Co2+ [Lu07] , Mn2+ [Lu07] , Fe2+ [Lu07] , Fe3+ [Lu07] , Ca2+ [Lu07] , Li+ [Lu07] , Al3+ [Lu07]

Inhibitors (Competitive): 5'-(dimethylsulfonio)-5'-deoxyadenosine [Tabor85, Pegg86] , ethylglyoxalbis(guanylhydrazone) [Tabor85, Pegg83] , methylglyoxalbis(guanylhydrazone) [Pegg83] , S-adenosyl 3-(methylthio)propylamine [Tabor85, Pegg83]

Inhibitors (Unknown Mechanism): 5'-(aminoiminomethyl)amino-5'-deoxyadenosine [Pegg86] , 5'-[(3-aminopropyl)-amino]-5'-deoxyadenosine [Pegg86] , 5'-[(3-aminopropyl)methylamino]-5'-deoxyadenosine [Pegg86] , 9-[6(S),9-diamino-5,6,7,8,9-pentadeoxy-β-D-ribo-nonafuranosyl]-9H-purin-6-amine [Pegg86] , 9-[6(RS)-C-carboxamido-5,6,7-trideoxy-β-D-ribo-octofuranosyl]-9H-purin-6-amine [Pegg86] , 9-[6(RS)-8-diamino-5,6,7,8-tetradeoxy-β-D-ribo-octofuranosyl]-9H-purin-6-amine [Pegg86] , Zn2+ [Lu07] , cyanoborohydride [Markham83] , phenylhydrazine [Markham82] , borohydride [Markham82] , spermidine [Tabor85, Kashiwagi88]

Primary Physiological Regulators of Enzyme Activity: spermidine

Subunit of adenosylmethionine decarboxylase: α cleavage product of SpeD

Synonyms: SpeD

Gene: speD Accession Numbers: EG10962 (MetaCyc), b0120, ECK0119

Sequence Length: 264 AAs

Molecular Weight: 30.385 kD (from nucleotide sequence)

pI: 5.44

GO Terms:

Biological Process: GO:0008295 - spermidine biosynthetic process Inferred from experiment [Tabor78]
Molecular Function: GO:0004014 - adenosylmethionine decarboxylase activity Inferred from experiment [Markham82]

MultiFun Terms: metabolism central intermediary metabolism polyamine biosynthesis

Subunit of adenosylmethionine decarboxylase: β cleavage product of SpeD

Synonyms: SpeD

Gene: speD Accession Numbers: EG10962 (MetaCyc), b0120, ECK0119

Sequence Length: 264 AAs

Molecular Weight: 30.385 kD (from nucleotide sequence)

pI: 5.44

MultiFun Terms: metabolism central intermediary metabolism polyamine biosynthesis

Peter D. Karp on Thu Nov 5, 2009:
Markus, A reminder to look into the case of speD and the roughly 5 other genes that have more than one product.

10/20/97 Gene b0120 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10962; confirmed by SwissProt match.


Anton87: Anton DL, Kutny R (1987). "Escherichia coli S-adenosylmethionine decarboxylase. Subunit structure, reductive amination, and NH2-terminal sequences." J Biol Chem 262(6);2817-22. PMID: 3546296

Anton87a: Anton DL, Kutny R (1987). "Mechanism of substrate inactivation of Escherichia coli S-adenosylmethionine decarboxylase." Biochemistry 26(20);6444-7. PMID: 3322380

Diaz91: Diaz E, Anton DL (1991). "Alkylation of an active-site cysteinyl residue during substrate-dependent inactivation of Escherichia coli S-adenosylmethionine decarboxylase." Biochemistry 1991;30(16);4078-81. PMID: 2018773

ECOSAL: EcoSal "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Kashiwagi88: Kashiwagi K, Igarashi K (1988). "Adjustment of polyamine contents in Escherichia coli." J Bacteriol 170(7);3131-5. PMID: 3290196

Li01: Li YF, Hess S, Pannell LK, White Tabor C, Tabor H (2001). "In vivo mechanism-based inactivation of S-adenosylmethionine decarboxylases from Escherichia coli, Salmonella typhimurium, and Saccharomyces cerevisiae." Proc Natl Acad Sci U S A 98(19);10578-83. PMID: 11526206

Lu07: Lu ZJ, Markham GD (2007). "Metal ion activation of S-adenosylmethionine decarboxylase reflects cation charge density." Biochemistry 46(27);8172-80. PMID: 17567041

Markham82: Markham GD, Tabor CW, Tabor H (1982). "S-adenosylmethionine decarboxylase of Escherichia coli. Studies on the covalently linked pyruvate required for activity." J Biol Chem 257(20);12063-8. PMID: 6749853

Markham83: Markham GD, Tabor CW, Tabor H (1983). "S-adenosylmethionine decarboxylase (Escherichia coli)." Methods Enzymol 1983;94;228-30. PMID: 6353153

Pegg83: Pegg AE, Jacobs G (1983). "Comparison of inhibitors of S-adenosylmethionine decarboxylase from different species." Biochem J 213(2);495-502. PMID: 6351843

Pegg86: Pegg AE, Coward JK, Talekar RR, Secrist JA (1986). "Effects of certain 5'-substituted adenosines on polyamine synthesis: selective inhibitors of spermine synthase." Biochemistry 1986;25(14);4091-7. PMID: 3091070

Tabor78: Tabor CW, Tabor H, Hafner EW (1978). "Escherichia coli mutants completely deficient in adenosylmethionine decarboxylase and in spermidine biosynthesis." J Biol Chem 253(10);3671-6. PMID: 348695

Tabor85: Tabor CW, Tabor H (1985). "Polyamines in microorganisms." Microbiol Rev 1985;49(1);81-99. PMID: 3157043

Tabor87: Tabor CW, Tabor H (1987). "The speEspeD operon of Escherichia coli. Formation and processing of a proenzyme form of S-adenosylmethionine decarboxylase." J Biol Chem 1987;262(33);16037-40. PMID: 3316212

Toms04: Toms AV, Kinsland C, McCloskey DE, Pegg AE, Ealick SE (2004). "Evolutionary links as revealed by the structure of Thermotoga maritima S-adenosylmethionine decarboxylase." J Biol Chem 279(32);33837-46. PMID: 15150268

Weitkamp91: Weitkamp EL, Dixon HB, Khomutov AR, Khomutov RM (1991). "Effect of magnesium ions on the inhibition of S-adenosylmethionine decarboxylase from Escherichia coli by [2-(amino-oxy)ethyl](5'-deoxyadenosin-5'-yl)(methyl)sulphonium." Biochem J 1991;277 ( Pt 3);643-5. PMID: 1872800

Wickner70: Wickner RB, Tabor CW, Tabor H (1970). "Purification of adenosylmethionine decarboxylase from Escherichia coli W: evidence for covalently bound pyruvate." J Biol Chem 245(8);2132-9. PMID: 4909563

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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