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Oxidoreductase PDB id
1h83
Jmol
Contents
Protein chains
459 a.a. *
Ligands
FAD ×3
DIA ×3
NAG-NAG ×2
NAG-NAG-FCA-MAN-
MAN
Waters ×734
* Residue conservation analysis
PDB id:
1h83
Name: Oxidoreductase
Title: Structure of polyamine oxidase in complex with 1,8-diaminooctane
Structure: Polyamine oxidase. Chain: a, b, c. Fragment: fad-binding domain. Ec: 1.5.3.11
Source: Zea mays. Maize. Organism_taxid: 4577
Biol. unit: Dimer (from PDB file)
Resolution:
1.90Å     R-factor:   0.196     R-free:   0.237
Authors: C.Binda,A.Coda,R.Angelini,R.Federico,P.Ascenzi,A.Mattevi
Key ref:
C.Binda et al. (2001). Structural bases for inhibitor binding and catalysis in polyamine oxidase. Biochemistry, 40, 2766-2776. PubMed id: 11258887 DOI: 10.1021/bi002751j
Date:
24-Jan-01     Release date:   31-Jan-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

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

 Enzyme reactions 
   Enzyme class 1: E.C.1.5.3.14  - Polyamine oxidase (propane-1,3-diamine-forming).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Spermidine + O2 + H2O = propane-1,3-diamine + 4-aminobutanal + H2O2
Spermidine
 + O(2)
 + H(2)O
 = propane-1,3-diamine
 +
4-aminobutanal
Bound ligand (Het Group name = NAG)
matches with 42.00% similarity 		+ H(2)O(2)
      Cofactor: FAD
FAD
Bound ligand (Het Group name = FAD) corresponds exactly
   Enzyme class 2: E.C.1.5.3.15  - 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
N(8)-acetylspermidine
 + O(2)
 + H(2)O
 = propane-1,3-diamine
 +
4-acetamidobutanal
Bound ligand (Het Group name = NAG)
matches with 64.00% similarity 		+ H(2)O(2)
      Cofactor: FAD
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   1 term 
  Biochemical function     oxidoreductase activity     3 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi002751j Biochemistry 40:2766-2776 (2001)
PubMed id: 11258887  
 
 
Structural bases for inhibitor binding and catalysis in polyamine oxidase.
C.Binda, R.Angelini, R.Federico, P.Ascenzi, A.Mattevi.
 
  ABSTRACT  
 
Polyamine oxidase (PAO) carries out the FAD-dependent oxidation of the secondary amino groups of spermidine and spermine, a key reaction in the polyamine catabolism. The active site of PAO consists of a 30 A long U-shaped catalytic tunnel, whose innermost part is located in front of the flavin ring. To provide insight into the PAO substrate specificity and amine oxidation mechanism, we have investigated the crystal structure of maize PAO in the reduced state and in complex with three different inhibitors, guazatine, 1,8-diaminooctane, and N(1)-ethyl-N(11)-[(cycloheptyl)methyl]-4,8-diazaundecane (CHENSpm). In the reduced state, the conformation of the isoalloxazine ring and the surrounding residues is identical to that of the oxidized enzyme. Only Lys300 moves away from the flavin to compensate for the change in cofactor protonation occurring upon reduction. The structure of the PAO.inhibitor complexes reveals an exact match between the inhibitors and the PAO catalytic tunnel. Inhibitor binding does not involve any protein conformational change. Such lock-and-key binding occurs also in the complex with CHENSpm, which forms a covalent adduct with the flavin N5 atom. Comparison of the enzyme complexes hints at an "out-of-register" mechanism of inhibition, in which the inhibitor secondary amino groups are not properly aligned with respect to the flavin to allow oxidation. Except for the Glu62-Glu170 pair, no negatively charged residues are involved in the recognition of substrate and inhibitor amino groups, which is in contrast to other polyamine binding proteins. This feature may be exploited in the design of drugs specifically targeting PAO.
 

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.  
20938508 D.Georgieva, M.Murakami, M.Perband, R.Arni, and C.Betzel (2011).
The structure of a native l-amino acid oxidase, the major component of the Vipera ammodytes ammodytes venomic, reveals dynamic active site and quaternary structure stabilization by divalent ions.
  Mol Biosyst, 7, 379-384.  
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.  
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
19911805 M.H.Pozzi, V.Gawandi, and P.F.Fitzpatrick (2009).
Mechanistic studies of para-substituted N,N'-dibenzyl-1,4-diaminobutanes as substrates for a mammalian polyamine oxidase.
  Biochemistry, 48, 12305-12313.  
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.  
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.  
16354669 A.Järvinen, T.A.Keinänen, N.A.Grigorenko, A.R.Khomutov, A.Uimari, J.Vepsäläinen, A.Närvänen, L.Alhonen, and J.Jänne (2006).
Guide molecule-driven stereospecific degradation of alpha-methylpolyamines by polyamine oxidase.
  J Biol Chem, 281, 4589-4595.  
16477020 A.Liavonchanka, E.Hornung, I.Feussner, and M.G.Rudolph (2006).
Structure and mechanism of the Propionibacterium acnes polyunsaturated fatty acid isomerase.
  Proc Natl Acad Sci U S A, 103, 2576-2581.
PDB codes: 2b9w 2b9x 2b9y 2ba9 2bab 2bac
16430210 A.Nagpal, M.P.Valley, P.F.Fitzpatrick, and A.M.Orville (2006).
Crystal structures of nitroalkane oxidase: insights into the reaction mechanism from a covalent complex of the flavoenzyme trapped during turnover.
  Biochemistry, 45, 1138-1150.
PDB codes: 2c0u 2c12
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.  
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
16799558 P.Stavropoulos, G.Blobel, and A.Hoelz (2006).
Crystal structure and mechanism of human lysine-specific demethylase-1.
  Nat Struct Mol Biol, 13, 626-632.
PDB code: 2h94
16956976 Y.Chen, Y.Yang, F.Wang, K.Wan, K.Yamane, Y.Zhang, and M.Lei (2006).
Crystal structure of human histone lysine-specific demethylase 1 (LSD1).
  Proc Natl Acad Sci U S A, 103, 13956-13961.
PDB code: 2hko
15889796 A.R.Khomutov, A.R.Simonian, J.Vespalainen, T.A.Keinanen, L.Alhonen, and J.Janne (2005).
[New oxaanalogues of spermine]
  Bioorg Khim, 31, 206-212.  
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.  
14705024 D.M.Smith, K.G.Daniel, Z.Wang, W.C.Guida, T.H.Chan, and Q.P.Dou (2004).
Docking studies and model development of tea polyphenol proteasome inhibitors: applications to rational drug design.
  Proteins, 54, 58-70.  
12192068 C.A.Bottoms, P.E.Smith, and J.J.Tanner (2002).
A structurally conserved water molecule in Rossmann dinucleotide-binding domains.
  Protein Sci, 11, 2125-2137.  
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.  
  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.  
12411496 S.Eimer, B.Lakowski, R.Donhauser, and R.Baumeister (2002).
Loss of spr-5 bypasses the requirement for the C.elegans presenilin sel-12 by derepressing hop-1.
  EMBO J, 21, 5787-5796.  
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.  
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 code is shown on the right.