title: A 30-angstrom-long U-shaped catalytic tunnel in the crystal structure of polyamine oxidase.
abstract: BACKGROUND
  Polyamines are essential for cell growth and differentiation; compounds interfering with their metabolism are potential anticancer agents. Polyamine oxidase (PAO) plays a central role in polyamine homeostasis. The enzyme utilises an FAD cofactor to catalyse the oxidation of the secondary amino groups of spermine and spermidine.
  
  
  RESULTS
  The first crystal structure of a polyamine oxidase has been determined to a resolution of 1.9 Angstroms. PAO from Zea mays contains two domains, which define a remarkable 30 Angstrom long U-shaped catalytic tunnel at their interface. The structure of PAO in complex with the inhibitor MDL72527 reveals the residues forming the catalytic machinery and unusual enzyme-inhibitor CH.O H bonds. A ring of glutamate and aspartate residues surrounding one of the two tunnel openings contributes to the steering of the substrate towards the inside of the tunnel.
  
  
  CONCLUSIONS
  PAO specifically oxidizes substrates that have both primary and secondary amino groups. The complex with MDL72527 shows that the primary amino groups are essential for the proper alignment of the substrate with respect to the flavin. Conservation of an N-terminal sequence motif indicates that PAO is member of a novel family of flavoenzymes. Among these, monoamine oxidase displays significant sequence homology with PAO, suggesting a similar overall folding topology.
authors.affiliation: Dipartimento di Genetica e Microbiologia, Università di Pavia, Via Abbiategrasso 207, I-27100 Pavia, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Binda
authors.forename: A
authors.initials: A
authors.lastname: Coda
authors.forename: R
authors.initials: R
authors.lastname: Angelini
authors.forename: R
authors.initials: R
authors.lastname: Federico
authors.forename: P
authors.initials: P
authors.lastname: Ascenzi
authors.forename: A
authors.initials: A
authors.lastname: Mattevi
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006031:Glycosylation; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008995:Monoamine Oxidase / Q000737:chemistry; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000037:antagonists & inhibitors / Q000737:chemistry*; D010940:Plant Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry*; D011073:Polyamines / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011700:Putrescine / Q000031:analogs & derivatives / Q000494:pharmacology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity; D003313:Zea mays / Q000201:enzymology; D000097667:Polyamine Oxidase
chemical_list: D004791:Enzyme Inhibitors; D005182:Flavin-Adenine Dinucleotide; D008995:Monoamine Oxidase; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010940:Plant Proteins; D011073:Polyamines; D011700:Putrescine; D000097667:Polyamine Oxidase; C044445:MDL 72527