title: The crystal structure of human S-adenosylmethionine decarboxylase at 2.25 A resolution reveals a novel fold.
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.
authors.affiliation: Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY 14853, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Ekstrom
authors.forename: I I
authors.initials: II
authors.lastname: Mathews
authors.forename: B A
authors.initials: BA
authors.lastname: Stanley
authors.forename: A E
authors.initials: AE
authors.lastname: Pegg
authors.forename: S E
authors.initials: SE
authors.lastname: Ealick
mesh_terms: D012437:Adenosylmethionine Decarboxylase / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D011700:Putrescine / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
chemical_list: D011994:Recombinant Proteins; D012437:Adenosylmethionine Decarboxylase; D011700:Putrescine