PDBsum entry 1b5q

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Oxidoreductase PDB id
Protein chains
459 a.a. *
FAD ×3
MD2 ×3
Waters ×628
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: A 30 angstrom u-shaped catalytic tunnel in the crystal struc polyamine oxidase
Structure: Protein (polyamine oxidase). Chain: a, b, c. Fragment: fad-binding domain
Source: Zea mays. Organism_taxid: 4577
Biol. unit: Dimer (from PQS)
1.90Å     R-factor:   0.193     R-free:   0.229
Authors: C.Binda,A.Coda,R.Angelini,R.Federico,P.Ascenzi,A.Mattevi
Key ref:
C.Binda et al. (1999). A 30-angstrom-long U-shaped catalytic tunnel in the crystal structure of polyamine oxidase. Structure Fold Des, 7, 265-276. PubMed id: 10368296 DOI: 10.1016/S0969-2126(99)80037-9
07-Jan-99     Release date:   07-Jan-00    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O64411  (PAO_MAIZE) -  Polyamine oxidase
500 a.a.
459 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class 1: E.C.  - Polyamine oxidase (propane-1,3-diamine-forming).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Spermidine + O2 + H2O = propane-1,3-diamine + 4-aminobutanal + H2O2
Bound ligand (Het Group name = MD2)
matches with 60.00% similarity
+ O(2)
+ H(2)O
= propane-1,3-diamine
Bound ligand (Het Group name = NAG)
matches with 42.86% similarity
+ H(2)O(2)
      Cofactor: FAD
Bound ligand (Het Group name = FAD) corresponds exactly
   Enzyme class 2: E.C.  - N(8)-acetylspermidine oxidase (propane-1,3-diamine-forming).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: N8-acetylspermidine + O2 + H2O = propane-1,3-diamine + 4-acetamidobutanal + H2O2
Bound ligand (Het Group name = MD2)
matches with 68.75% similarity
+ O(2)
+ H(2)O
= propane-1,3-diamine
Bound ligand (Het Group name = NAG)
matches with 64.29% similarity
+ H(2)O(2)
      Cofactor: FAD
Bound ligand (Het Group name = FAD) corresponds exactly
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     N1-acetylspermine:oxygen oxidoreductase (propane-1,3-diamine-forming) activity     8 terms  


DOI no: 10.1016/S0969-2126(99)80037-9 Structure Fold Des 7:265-276 (1999)
PubMed id: 10368296  
A 30-angstrom-long U-shaped catalytic tunnel in the crystal structure of polyamine oxidase.
C.Binda, A.Coda, R.Angelini, R.Federico, P.Ascenzi, A.Mattevi.
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.
  Selected figure(s)  
Figure 6.
Figure 6. Schematic drawing of the interactions between FAD and the protein. Hydrogen bonds are indicated by dashed lines. The interatomic distances are in angstroms. W indicates ordered water molecules.
  The above figure is reprinted by permission from Cell Press: Structure Fold Des (1999, 7, 265-276) copyright 1999.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21205212 A.Fiorillo, R.Federico, F.Polticelli, A.Boffi, F.Mazzei, M.Di Fusco, A.Ilari, and P.Tavladoraki (2011).
The structure of maize polyamine oxidase K300M mutant in complex with the natural substrates provides a snapshot of the catalytic mechanism of polyamine oxidation.
  FEBS J, 278, 809-821.  
20839014 P.Tavladoraki, M.Cervelli, F.Antonangeli, G.Minervini, P.Stano, R.Federico, P.Mariottini, and F.Polticelli (2011).
Probing mammalian spermine oxidase enzyme-substrate complex through molecular modeling, site-directed mutagenesis and biochemical characterization.
  Amino Acids, 40, 1115-1126.  
20946629 M.Cervelli, G.Bellavia, E.Fratini, R.Amendola, F.Polticelli, M.Barba, R.Federico, F.Signore, G.Gucciardo, R.Grillo, P.M.Woster, R.A.Casero, and P.Mariottini (2010).
Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm.
  BMC Cancer, 10, 555.  
20000632 M.S.Adachi, P.R.Juarez, and P.F.Fitzpatrick (2010).
Mechanistic studies of human spermine oxidase: kinetic mechanism and pH effects.
  Biochemistry, 49, 386-392.  
20353187 M.S.Jorns, Z.W.Chen, and F.S.Mathews (2010).
Structural characterization of mutations at the oxygen activation site in monomeric sarcosine oxidase .
  Biochemistry, 49, 3631-3639.
PDB codes: 3m0o 3m12 3m13
19651103 P.F.Fitzpatrick (2010).
Oxidation of amines by flavoproteins.
  Arch Biochem Biophys, 493, 13-25.  
20532512 Y.Takahashi, R.Cong, G.H.Sagor, M.Niitsu, T.Berberich, and T.Kusano (2010).
Characterization of five polyamine oxidase isoforms in Arabidopsis thaliana.
  Plant Cell Rep, 29, 955-965.  
19624733 F.Forneris, E.Battaglioli, A.Mattevi, and C.Binda (2009).
New roles of flavoproteins in molecular cell biology: histone demethylase LSD1 and chromatin.
  FEBS J, 276, 4304-4312.  
19459938 F.Forneris, R.Orru, D.Bonivento, L.R.Chiarelli, and A.Mattevi (2009).
ThermoFAD, a Thermofluor-adapted flavin ad hoc detection system for protein folding and ligand binding.
  FEBS J, 276, 2833-2840.  
19408960 H.Gaweska, M.Henderson Pozzi, D.M.Schmidt, D.G.McCafferty, and P.F.Fitzpatrick (2009).
Use of pH and kinetic isotope effects to establish chemistry as rate-limiting in oxidation of a peptide substrate by LSD1.
  Biochemistry, 48, 5440-5445.  
19531050 J.Arima, C.Sasaki, C.Sakaguchi, H.Mizuno, T.Tamura, A.Kashima, H.Kusakabe, S.Sugio, and K.Inagaki (2009).
Structural characterization of L-glutamate oxidase from Streptomyces sp. X-119-6.
  FEBS J, 276, 3894-3903.
PDB code: 2e1m
19199575 M.Henderson Pozzi, V.Gawandi, and P.F.Fitzpatrick (2009).
pH dependence of a mammalian polyamine oxidase: insights into substrate specificity and the role of lysine 315.
  Biochemistry, 48, 1508-1516.  
19243237 T.Senda, M.Senda, S.Kimura, and T.Ishida (2009).
Redox control of protein conformation in flavoproteins.
  Antioxid Redox Signal, 11, 1741-1766.  
18183391 E.W.van Hellemond, M.van Dijk, D.P.Heuts, D.B.Janssen, and M.W.Fraaije (2008).
Discovery and characterization of a putrescine oxidase from Rhodococcus erythropolis NCIMB 11540.
  Appl Microbiol Biotechnol, 78, 455-463.  
18693755 G.Zhao, R.C.Bruckner, and M.S.Jorns (2008).
Identification of the oxygen activation site in monomeric sarcosine oxidase: role of Lys265 in catalysis.
  Biochemistry, 47, 9124-9135.  
  18323603 K.E.Atkin, R.Reiss, N.J.Turner, A.M.Brzozowski, and G.Grogan (2008).
Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of variants of monoamine oxidase from Aspergillus niger.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 182-185.  
18422650 T.Murray-Stewart, Y.Wang, A.Goodwin, A.Hacker, A.Meeker, and R.A.Casero (2008).
Nuclear localization of human spermine oxidase isoforms - possible implications in drug response and disease etiology.
  FEBS J, 275, 2795-2806.  
17542620 E.C.Ralph, J.S.Hirschi, M.A.Anderson, W.W.Cleland, D.A.Singleton, and P.F.Fitzpatrick (2007).
Insights into the mechanism of flavoprotein-catalyzed amine oxidation from nitrogen isotope effects on the reaction of N-methyltryptophan oxidase.
  Biochemistry, 46, 7655-7664.  
17401536 M.A.Akyüz, S.S.Erdem, and D.E.Edmondson (2007).
The aromatic cage in the active site of monoamine oxidase B: effect on the structural and electronic properties of bound benzylamine and p-nitrobenzylamine.
  J Neural Transm, 114, 693-698.  
17385064 M.Sebela, M.Tylichová, and P.Pec (2007).
Inhibition of diamine oxidases and polyamine oxidases by diamine-based compounds.
  J Neural Transm, 114, 793-798.  
  19890477 P.F.Fitzpatrick (2007).
Insights into the mechanisms of flavoprotein oxidases from kinetic isotope effects.
  J Labelled Comp Radiopharm, 50, 1016-1025.  
16225993 A.Toninello, P.Pietrangeli, U.De Marchi, M.Salvi, and B.Mondovì (2006).
Amine oxidases in apoptosis and cancer.
  Biochim Biophys Acta, 1765, 1.  
17176107 E.C.Ralph, M.A.Anderson, W.W.Cleland, and P.F.Fitzpatrick (2006).
Mechanistic studies of the flavoenzyme tryptophan 2-monooxygenase: deuterium and 15N kinetic isotope effects on alanine oxidation by an L-amino acid oxidase.
  Biochemistry, 45, 15844-15852.  
17046020 I.M.Moustafa, S.Foster, A.Y.Lyubimov, and A.Vrielink (2006).
Crystal structure of LAAO from Calloselasma rhodostoma with an L-phenylalanine substrate: insights into structure and mechanism.
  J Mol Biol, 364, 991.
PDB code: 2iid
16519678 M.Bianchi, F.Polticelli, P.Ascenzi, M.Botta, R.Federico, P.Mariottini, and A.Cona (2006).
Inhibition of polyamine and spermine oxidases by polyamine analogues.
  FEBS J, 273, 1115-1123.  
16879612 M.Cervelli, M.Bianchi, A.Cona, C.Crosatti, M.Stanca, R.Angelini, R.Federico, and P.Mariottini (2006).
Barley polyamine oxidase isoforms 1 and 2, a peculiar case of gene duplication.
  FEBS J, 273, 3990-4002.  
16914725 M.G.Lee, C.Wynder, D.A.Bochar, M.A.Hakimi, N.Cooch, and R.Shiekhattar (2006).
Functional interplay between histone demethylase and deacetylase enzymes.
  Mol Cell Biol, 26, 6395-6402.  
16885027 M.Yang, C.B.Gocke, X.Luo, D.Borek, D.R.Tomchick, M.Machius, Z.Otwinowski, and H.Yu (2006).
Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase.
  Mol Cell, 23, 377-387.
PDB code: 2iw5
16531230 N.Tochio, T.Umehara, S.Koshiba, M.Inoue, T.Yabuki, M.Aoki, E.Seki, S.Watanabe, Y.Tomo, M.Hanada, M.Ikari, M.Sato, T.Terada, T.Nagase, O.Ohara, M.Shirouzu, A.Tanaka, T.Kigawa, and S.Yokoyama (2006).
Solution structure of the SWIRM domain of human histone demethylase LSD1.
  Structure, 14, 457-468.
PDB code: 2com
15578214 A.Cona, S.Moreno, F.Cenci, R.Federico, and R.Angelini (2005).
Cellular re-distribution of flavin-containing polyamine oxidase in differentiating root and mesocotyl of Zea mays L. seedlings.
  Planta, 221, 265-276.  
16275925 C.Siebold, N.Berrow, T.S.Walter, K.Harlos, R.J.Owens, D.I.Stuart, J.R.Terman, A.L.Kolodkin, R.J.Pasterkamp, and E.Y.Jones (2005).
High-resolution structure of the catalytic region of MICAL (molecule interacting with CasL), a multidomain flavoenzyme-signaling molecule.
  Proc Natl Acad Sci U S A, 102, 16836-16841.
PDB codes: 2bry 2c4c
15723552 E.C.Ralph, and P.F.Fitzpatrick (2005).
pH and kinetic isotope effects on sarcosine oxidation by N-methyltryptophan oxidase.
  Biochemistry, 44, 3074-3081.  
15955064 M.Bianchi, R.Amendola, R.Federico, F.Polticelli, and P.Mariottini (2005).
Two short protein domains are responsible for the nuclear localization of the mouse spermine oxidase mu isoform.
  FEBS J, 272, 3052-3059.  
16079794 M.G.Lee, C.Wynder, N.Cooch, and R.Shiekhattar (2005).
An essential role for CoREST in nucleosomal histone 3 lysine 4 demethylation.
  Nature, 437, 432-435.  
15865452 M.Royo, and P.F.Fitzpatrick (2005).
Mechanistic studies of mouse polyamine oxidase with N1,N12-bisethylspermine as a substrate.
  Biochemistry, 44, 7079-7084.  
15791459 Y.Wang, A.Hacker, T.Murray-Stewart, B.Frydman, A.Valasinas, A.V.Fraser, P.M.Woster, and R.A.Casero (2005).
Properties of recombinant human N1-acetylpolyamine oxidase (hPAO): potential role in determining drug sensitivity.
  Cancer Chemother Pharmacol, 56, 83-90.  
15189875 J.D.Lawson, E.Pate, I.Rayment, and R.G.Yount (2004).
Molecular dynamics analysis of structural factors influencing back door pi release in myosin.
  Biophys J, 86, 3794-3803.  
14764092 M.Cervelli, A.Bellini, M.Bianchi, L.Marcocci, S.Nocera, F.Polticelli, R.Federico, R.Amendola, and P.Mariottini (2004).
Mouse spermine oxidase gene splice variants. Nuclear subcellular localization of a novel active isoform.
  Eur J Biochem, 271, 760-770.  
15469498 M.Cervelli, O.Di Caro, A.Di Penta, R.Angelini, R.Federico, A.Vitale, and P.Mariottini (2004).
A novel C-terminal sequence from barley polyamine oxidase is a vacuolar sorting signal.
  Plant J, 40, 410-418.  
12912903 D.Leys, J.Basran, and N.S.Scrutton (2003).
Channelling and formation of 'active' formaldehyde in dimethylglycine oxidase.
  EMBO J, 22, 4038-4048.
PDB codes: 1pj5 1pj6 1pj7
12458219 M.Cervelli, F.Polticelli, R.Federico, and P.Mariottini (2003).
Heterologous expression and characterization of mouse spermine oxidase.
  J Biol Chem, 278, 5271-5276.  
12660232 T.Wu, V.Yankovskaya, and W.S.McIntire (2003).
Cloning, sequencing, and heterologous expression of the murine peroxisomal flavoprotein, N1-acetylated polyamine oxidase.
  J Biol Chem, 278, 20514-20525.  
14593187 Y.He, S.D.Michaels, and R.M.Amasino (2003).
Regulation of flowering time by histone acetylation in Arabidopsis.
  Science, 302, 1751-1754.  
12015330 C.Binda, A.Mattevi, and D.E.Edmondson (2002).
Structure-function relationships in flavoenzyme-dependent amine oxidations: a comparison of polyamine oxidase and monoamine oxidase.
  J Biol Chem, 277, 23973-23976.  
11753429 C.Binda, P.Newton-Vinson, F.Hubálek, D.E.Edmondson, and A.Mattevi (2002).
Structure of human monoamine oxidase B, a drug target for the treatment of neurological disorders.
  Nat Struct Biol, 9, 22-26.
PDB code: 1gos
  12186646 L.Aravind, and L.M.Iyer (2002).
The SWIRM domain: a conserved module found in chromosomal proteins points to novel chromatin-modifying activities.
  Genome Biol, 3, RESEARCH0039.  
11705021 A.Radová, M.Sebela, P.Galuszka, I.Frébort, S.Jacobsen, H.G.Faulhammer, and P.Pec (2001).
Barley polyamine oxidase: characterisation and analysis of the cofactor and the N-terminal amino acid sequence.
  Phytochem Anal, 12, 166-173.  
11258887 C.Binda, R.Angelini, R.Federico, P.Ascenzi, and A.Mattevi (2001).
Structural bases for inhibitor binding and catalysis in polyamine oxidase.
  Biochemistry, 40, 2766-2776.
PDB codes: 1h81 1h82 1h83 1h84 1h86
11432750 M.Cervelli, A.Cona, R.Angelini, F.Polticelli, R.Federico, and P.Mariottini (2001).
A barley polyamine oxidase isoform with distinct structural features and subcellular localization.
  Eur J Biochem, 268, 3816-3830.  
11514662 O.Dym, and D.Eisenberg (2001).
Sequence-structure analysis of FAD-containing proteins.
  Protein Sci, 10, 1712-1728.  
11260159 P.Iacovacci, C.Pini, C.Afferni, B.Barletta, R.Tinghino, E.Schininà, R.Federico, A.Mari, and G.Di Felice (2001).
A monoclonal antibody specific for a carbohydrate epitope recognizes an IgE-binding determinant shared by taxonomically unrelated allergenic pollens.
  Clin Exp Allergy, 31, 458-465.  
11157233 Y.Liu, T.M.Louie, J.Payne, J.Bohuslavek, H.Bolton, and L.Xun (2001).
Identification, purification, and characterization of iminodiacetate oxidase from the EDTA-degrading bacterium BNC1.
  Appl Environ Microbiol, 67, 696-701.  
10962107 E.Varela, M.Jesús Martínez, and A.T.Martínez (2000).
Aryl-alcohol oxidase protein sequence: a comparison with glucose oxidase and other FAD oxidoreductases.
  Biochim Biophys Acta, 1481, 202-208.
PDB code: 1qjn
10944103 P.D.Pawelek, J.Cheah, R.Coulombe, P.Macheroux, S.Ghisla, and A.Vrielink (2000).
The structure of L-amino acid oxidase reveals the substrate trajectory into an enantiomerically conserved active site.
  EMBO J, 19, 4204-4215.
PDB codes: 1f8r 1f8s
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.