View the latest EBI news stories and important announcements...

Search The CSA
EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1jen

E.C. nameadenosylmethionine decarboxylase
SpeciesHomo sapiens (Human)
E.C. Number (IntEnz)
CSA Homologues of 1jen1i72,1i79,1i7b,1i7c,1i7m,1jl0,1mhm,1msv,
CSA Entries With UniProtID P17707
CSA Entries With EC Number
PDBe Entry 1jen
PDBSum Entry 1jen
MACiE Entry 1jen

Literature Report

IntroductionS-Adenosylmethionine decarboxylase (AdoMetDC) is a critical regulatory enzyme in the polyamine synthetic pathway, and has been the subject of biochemical studies spanning several decades. AdoMetDC is a target for drug design against cancer, parasitic infection, and a variety of hyperproliferative disorders and has several intriguing biochemical features such as an unusual self-cleavage reaction, a covalently bound reactive pyruvoyl group, allosteric activation, and high in vivo degradation rates.
AdoMetDC catalyses the removal of the carboxylate group from S-adenosylmethionine (AdoMet) to form (5-deoxy-5-adenosyl)(3-aminopropyl) methylsulfonium salt (dcAdoMet), which is committed to act as the n-propylamine group donor for the synthesis of the polyamines spermidine and spermine from the diamine putrescine. These polyamines have been shown to be involved in the initiation and maintenance of proliferative states, and are crucial for cell growth and differentiation. AdoMetDC is a control point within the polyamine pathway, and its activity is highly regulated during the cell cycle via multiple mechanisms. Deregulation of this pathway has been associated with several types of cancers. The unusual catalytic mechanism of AdoMetDC involves a covalently bound pyruvoyl group instead of the cofactor pyridoxal-5-phosphate (PLP). This pyruvoyl group is generated in a post-translation modification internal serinolysis reaction.
MechansimThe pyruvoyl moiety functions as an electron sink for the catalytic decarboxylation reaction in a manner similar to that of the cofactor PLP. The substrate AdoMet binds to the enzyme through a Schiff base to the active site pyruvoyl group. The decarboxylation reaction proceeds with the pair of electrons from the leaving group (CO2 ) delocalised into the pyruvoyl group. An acidic residue, likely Cys82, protonates the C-alpha carbon of the substrate to generate the imine intermediate. The imine is further hydrolysed to release the product dcAdoMet.

Catalytic Sites for 1jen

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
CysA8282macie:sideChainActs as a general acid to protonate C-alpha carbon to generate the imine intermediate in order to form the product , not the competing transamination reaction.
PyrA680macie:ptmBinds to substrate to form Schiff base linkage and acts as the electron sink throughout the reaction.

Literature References

Notes:Note residues His243 and Ser229 are only implicated int he pyruvate forming modification not int eh decarboylation reaction. Glu11 could potentially form a proton relay with Cys82 in order to protonate C-alpha, however no exisiting experimental evidence for this.
Xiong H
Role of cysteine-82 in the catalytic mechanism of human S-adenosylmethionine decarboxylase.
Biochemistry 1999 38 2462-2470
PubMed: 10029540
Ekstrom JL
The crystal structure of human S-adenosylmethionine decarboxylase at 2.25 A resolution reveals a novel fold.
Structure 1999 7 583-595
PubMed: 10378277
Bale S
Structural biology of S-adenosylmethionine decarboxylase.
Amino Acids 2010 38 451-460
PubMed: 19997761