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PDBsum entry 1jen

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protein Protein-protein interface(s) links
S-adenosylmethionine decarboxylase PDB id
1jen
Jmol
Contents
Protein chains
57 a.a. *
249 a.a. *
54 a.a. *
Waters ×414
* Residue conservation analysis
PDB id:
1jen
Name: S-adenosylmethionine decarboxylase
Title: Human s-adenosylmethionine decarboxylase
Structure: Protein (s-adenosylmethionine decarboxylase (beta chain)). Chain: b, d. Synonym: adometdc, samdc. Engineered: yes. Protein (s-adenosylmethionine decarboxylase (alpha chain)). Chain: a, c. Synonym: adometdc, samdc.
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
Biol. unit: Hetero-Dimer (from PDB file)
Resolution:
2.25Å     R-factor:   0.177     R-free:   0.229
Authors: J.L.Ekstrom,I.I.Mathews,B.A.Stanley,A.E.Pegg,S.E.Ealick
Key ref:
J.L.Ekstrom et al. (1999). The crystal structure of human S-adenosylmethionine decarboxylase at 2.25 A resolution reveals a novel fold. Structure, 7, 583-595. PubMed id: 10378277 DOI: 10.1016/S0969-2126(99)80074-4
Date:
23-Feb-99     Release date:   01-Jun-99    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P17707  (DCAM_HUMAN) -  S-adenosylmethionine decarboxylase proenzyme
Seq:
Struc:
334 a.a.
57 a.a.
Protein chains
Pfam   ArchSchema ?
P17707  (DCAM_HUMAN) -  S-adenosylmethionine decarboxylase proenzyme
Seq:
Struc:
334 a.a.
249 a.a.*
Protein chain
Pfam   ArchSchema ?
P17707  (DCAM_HUMAN) -  S-adenosylmethionine decarboxylase proenzyme
Seq:
Struc:
334 a.a.
54 a.a.
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: Chains B, A, D, C: E.C.4.1.1.50  - Adenosylmethionine decarboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Spermine Biosynthesis
      Reaction: S-adenosyl-L-methionine = S-adenosyl 3-(methylthio)propylamine + CO2
S-adenosyl-L-methionine
= S-adenosyl 3-(methylthio)propylamine
+ CO(2)
      Cofactor: Pyruvate
Pyruvate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     spermine biosynthetic process   2 terms 
  Biochemical function     adenosylmethionine decarboxylase activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1016/S0969-2126(99)80074-4 Structure 7:583-595 (1999)
PubMed id: 10378277  
 
 
The crystal structure of human S-adenosylmethionine decarboxylase at 2.25 A resolution reveals a novel fold.
J.L.Ekstrom, I.I.Mathews, B.A.Stanley, A.E.Pegg, S.E.Ealick.
 
  ABSTRACT  
 
BACKGROUND: S-Adenosylmethionine decarboxylase (AdoMetDC) is a critical regulatory enzyme of the polyamine synthetic pathway, and a well-studied drug target. The AdoMetDC decarboxylation reaction depends upon a pyruvoyl cofactor generated via an intramolecular proenzyme self-cleavage reaction. Both the proenzyme-processing and substrate-decarboxylation reactions are allosterically enhanced by putrescine. Structural elucidation of this enzyme is necessary to fully interpret the existing mutational and inhibitor-binding data, and to suggest further experimental studies. RESULTS: The structure of human AdoMetDC has been determined to 2.25 A resolution using multiwavelength anomalous diffraction (MAD) phasing methods based on 22 selenium-atom positions. The quaternary structure of the mature AdoMetDC is an (alpha beta)2 dimer, where alpha and beta represent the products of the proenzyme self-cleavage reaction. The architecture of each (alpha beta) monomer is a novel four-layer alpha/beta-sandwich fold, comprised of two antiparallel eight-stranded beta sheets flanked by several alpha and 3(10) helices. CONCLUSIONS: The structure and topology of AdoMetDC display internal symmetry, suggesting that this protein may be the product of an ancient gene duplication. The positions of conserved, functionally important residues suggest the location of the active site and a possible binding site for the effector molecule putrescine.
 
  Selected figure(s)  
 
Figure 8.
Figure 8. Mechanisms of the proenzyme processing and catalytic reactions. (a) Mechanism of the AdoMetDC proteolytic proenzyme processing reaction. (b) Mechanism of the AdoMetDC pyruvoyl-dependent decarboxylation reaction.
 
  The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 583-595) copyright 1999.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20512387 G.Colotti, and A.Ilari (2011).
Polyamine metabolism in Leishmania: from arginine to trypanothione.
  Amino Acids, 40, 269-285.  
20693694 H.Xu (2010).
Enhancing MAD F(A) data for substructure determination.
  Acta Crystallogr D Biol Crystallogr, 66, 945-949.  
21048303 M.Wada, and A.Shirahata (2010).
Conformational stabilization of rat s-adenosylmethionine decarboxylase by putrescine.
  Biol Pharm Bull, 33, 1800-1805.  
20124698 S.Bale, K.Baba, D.E.McCloskey, A.E.Pegg, and S.E.Ealick (2010).
Complexes of Thermotoga maritimaS-adenosylmethionine decarboxylase provide insights into substrate specificity.
  Acta Crystallogr D Biol Crystallogr, 66, 181-189.
PDB codes: 3iwb 3iwc 3iwd
19997761 S.Bale, and S.E.Ealick (2010).
Structural biology of S-adenosylmethionine decarboxylase.
  Amino Acids, 38, 451-460.  
19209891 D.E.McCloskey, S.Bale, J.A.Secrist, A.Tiwari, T.H.Moss, J.Valiyaveettil, W.H.Brooks, W.C.Guida, A.E.Pegg, and S.E.Ealick (2009).
New insights into the design of inhibitors of human S-adenosylmethionine decarboxylase: studies of adenine C8 substitution in structural analogues of S-adenosylmethionine.
  J Med Chem, 52, 1388-1407.
PDB codes: 3dz2 3dz3 3dz4 3dz5 3dz6 3dz7
19523496 E.K.Willert, and M.A.Phillips (2009).
Cross-species activation of trypanosome S-adenosylmethionine decarboxylase by the regulatory subunit prozyme.
  Mol Biochem Parasitol, 168, 1-6.  
19527050 S.Bale, W.Brooks, J.W.Hanes, A.M.Mahesan, W.C.Guida, and S.E.Ealick (2009).
Role of the sulfonium center in determining the ligand specificity of human s-adenosylmethionine decarboxylase.
  Biochemistry, 48, 6423-6430.
PDB codes: 3h0v 3h0w
18367445 H.Wu, J.Min, H.Zeng, D.E.McCloskey, Y.Ikeguchi, P.Loppnau, A.J.Michael, A.E.Pegg, and A.N.Plotnikov (2008).
Crystal structure of human spermine synthase: implications of substrate binding and catalytic mechanism.
  J Biol Chem, 283, 16135-16146.
PDB codes: 3c6k 3c6m
18219117 H.Xu, and C.M.Weeks (2008).
Rapid and automated substructure solution by Shake-and-Bake.
  Acta Crystallogr D Biol Crystallogr, 64, 172-177.  
19053272 S.Bale, M.M.Lopez, G.I.Makhatadze, Q.Fang, A.E.Pegg, and S.E.Ealick (2008).
Structural basis for putrescine activation of human S-adenosylmethionine decarboxylase.
  Biochemistry, 47, 13404-13417.
PDB codes: 3ep3 3ep4 3ep5 3ep6 3ep7 3ep8 3ep9 3epa 3epb
15983421 H.Xu, C.M.Weeks, and H.A.Hauptman (2005).
Optimizing statistical Shake-and-Bake for Se-atom substructure determination.
  Acta Crystallogr D Biol Crystallogr, 61, 976-981.  
16225687 P.Z.Kozbial, and A.R.Mushegian (2005).
Natural history of S-adenosylmethionine-binding proteins.
  BMC Struct Biol, 5, 19.  
15150268 A.V.Toms, C.Kinsland, D.E.McCloskey, A.E.Pegg, and S.E.Ealick (2004).
Evolutionary links as revealed by the structure of Thermotoga maritima S-adenosylmethionine decarboxylase.
  J Biol Chem, 279, 33837-33846.
PDB codes: 1tlu 1tmi
14718534 A.Yerlikaya, and B.A.Stanley (2004).
S-adenosylmethionine decarboxylase degradation by the 26 S proteasome is accelerated by substrate-mediated transamination.
  J Biol Chem, 279, 12469-12478.  
15274916 H.Nishimasu, S.Fushinobu, H.Shoun, and T.Wakagi (2004).
The first crystal structure of the novel class of fructose-1,6-bisphosphatase present in thermophilic archaea.
  Structure, 12, 949-959.
PDB code: 1umg
14573607 Z.J.Lu, and G.D.Markham (2004).
Catalytic properties of the archaeal S-adenosylmethionine decarboxylase from Methanococcus jannaschii.
  J Biol Chem, 279, 265-273.  
12674502 D.Ndjonka, A.Da'dara, R.D.Walter, and K.Lüersen (2003).
Caenorhabditis elegans S-adenosylmethionine decarboxylase is highly stimulated by putrescine but exhibits a low specificity for activator binding.
  Biol Chem, 384, 83-91.  
12974388 D.Ndjonka, Y.Zou, X.Bi, P.Woster, R.D.Walter, and K.Lüersen (2003).
The activator-binding site of Onchocerca volvulus S-adenosylmethionine decarboxylase, a potential drug target.
  Biol Chem, 384, 1195-1201.  
14633979 F.Schmitzberger, M.L.Kilkenny, C.M.Lobley, M.E.Webb, M.Vinkovic, D.Matak-Vinkovic, M.Witty, D.Y.Chirgadze, A.G.Smith, C.Abell, and T.L.Blundell (2003).
Structural constraints on protein self-processing in L-aspartate-alpha-decarboxylase.
  EMBO J, 22, 6193-6204.
PDB codes: 1ppy 1pqe 1pqf 1pqh 1pt0 1pt1 1pyq 1pyu
12557188 L.Birkholtz, F.Joubert, A.W.Neitz, and A.I.Louw (2003).
Comparative properties of a three-dimensional model of Plasmodium falciparum ornithine decarboxylase.
  Proteins, 50, 464-473.
PDB code: 1m9v
11422384 B.Bednarski, J.R.Andreesen, and A.Pich (2001).
In vitro processing of the proproteins GrdE of protein B of glycine reductase and PrdA of D-proline reductase from Clostridium sticklandii: formation of a pyruvoyl group from a cysteine residue.
  Eur J Biochem, 268, 3538-3544.  
11526206 Y.F.Li, S.Hess, L.K.Pannell, C.White Tabor, and H.Tabor (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, 10578-10583.  
11073910 A.D.Kim, D.E.Graham, S.H.Seeholzer, and G.D.Markham (2000).
S-Adenosylmethionine decarboxylase from the archaeon Methanococcus jannaschii: identification of a novel family of pyruvoyl enzymes.
  J Bacteriol, 182, 6667-6672.  
11006535 S.E.Ealick (2000).
Advances in multiple wavelength anomalous diffraction crystallography.
  Curr Opin Chem Biol, 4, 495-499.  
10425674 A.M.Deacon, and S.E.Ealick (1999).
Selenium-based MAD phasing: setting the sites on larger structures.
  Structure, 7, R161-R166.  
10574985 H.Xiong, and A.E.Pegg (1999).
Mechanistic studies of the processing of human S-adenosylmethionine decarboxylase proenzyme. Isolation of an ester intermediate.
  J Biol Chem, 274, 35059-35066.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.