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Oxidoreductase PDB id
1d6y
Jmol
Contents
Protein chains
718 a.a. *
Ligands
HY1 ×2
_NO ×2
PEA
GOL ×2
Metals
_CU ×2
_CA ×4
Waters ×1427
* Residue conservation analysis
PDB id:
1d6y
Name: Oxidoreductase
Title: Crystal structure of e. Coli copper-containing amine oxidase anaerobically reduced with beta-phenylethylamine and comple nitric oxide.
Structure: Copper amine oxidase. Chain: a, b. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Biol. unit: Dimer (from PQS)
Resolution:
2.40Å     R-factor:   0.181     R-free:   0.231
Authors: C.M.Wilmot,J.Hajdu,M.J.Mcpherson,P.F.Knowles,S.E.V.Phillips
Key ref:
C.M.Wilmot et al. (1999). Visualization of dioxygen bound to copper during enzyme catalysis. Science, 286, 1724-1728. PubMed id: 10576737 DOI: 10.1126/science.286.5445.1724
Date:
16-Oct-99     Release date:   02-Feb-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P46883  (AMO_ECOLI) -  Primary amine oxidase
Seq:
Struc: 		 
Seq:
Struc: 		757 a.a.
719 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.1.4.3.21  - Primary-amine oxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RCH2NH2 + H2O + O2 = RCHO + NH3 + H2O2
RCH(2)NH(2)
 + H(2)O
 + O(2)
 = RCHO
 + NH(3)
 + H(2)O(2)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     periplasmic space   1 term 
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     tryptamine:oxygen oxidoreductase (deaminating) activity     9 terms  

 

 
    reference    
 
 
DOI no: 10.1126/science.286.5445.1724 Science 286:1724-1728 (1999)
PubMed id: 10576737  
 
 
Visualization of dioxygen bound to copper during enzyme catalysis.
C.M.Wilmot, J.Hajdu, M.J.McPherson, P.F.Knowles, S.E.Phillips.
 
  ABSTRACT  
 
X-ray crystal structures of three species related to the oxidative half of the reaction of the copper-containing quinoprotein amine oxidase from Escherichia coli have been determined. Crystals were freeze-trapped either anaerobically or aerobically after exposure to substrate, and structures were determined to resolutions between 2.1 and 2.4 angstroms. The oxidation state of the quinone cofactor was investigated by single-crystal spectrophotometry. The structures reveal the site of bound dioxygen and the proton transfer pathways involved in oxygen reduction. The quinone cofactor is regenerated from the iminoquinone intermediate by hydrolysis involving Asp383, the catalytic base in the reductive half-reaction. Product aldehyde inhibits the hydrolysis, making release of product the rate-determining step of the reaction in the crystal.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. (A) Ribbon diagram of ECAO homodimer (30). One monomer is colored red and the other is colored by domains (D1, cyan; D2, magenta; D3, royal blue; D4, light blue). Copper ions are shown as green spheres. (B) Schematic of ECAO active site, showing the copper ion-ligand geometry and major TPQ conformation (31). The water axial and equatorial ligands to the copper ion are labeled Wa and We, respectively. We is mobile and its position is not always fully occupied in CuAO structures. 		Figure 3.
Fig. 3. Overview of the essential features of the active sites of the crystal structures (30). (A) Anaerobic -phenylethylamine-reduced ECAO. (B) Complex of anaerobic -phenylethylamine-reduced ECAO with nitric oxide. (C) Equilibrium turnover species in the crystal by flash-freezing after exposure to -phenylethylamine, highlighting the proposed mechanistic features of the oxidative half-reaction contained in the structure. Dashed lines indicate key interactions. Red spheres represent mechanistic waters.
 
  The above figures are reprinted by permission from the AAAs: Science (1999, 286, 1724-1728) copyright 1999.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21525643 A.M.Orville, R.Buono, M.Cowan, A.Héroux, G.Shea-McCarthy, D.K.Schneider, J.M.Skinner, M.J.Skinner, D.Stoner-Ma, and R.M.Sweet (2011).
Correlated single-crystal electronic absorption spectroscopy and X-ray crystallography at NSLS beamline X26-C.
  J Synchrotron Radiat, 18, 358-366.  
20155950 C.M.Chang, V.J.Klema, B.J.Johnson, M.Mure, J.P.Klinman, and C.M.Wilmot (2010).
Kinetic and structural analysis of substrate specificity in two copper amine oxidases from Hansenula polymorpha.
  Biochemistry, 49, 2540-2550.
PDB code: 3loy
19133805 A.M.Orville, G.T.Lountos, S.Finnegan, G.Gadda, and R.Prabhakar (2009).
Crystallographic, spectroscopic, and computational analysis of a flavin C4a-oxygen adduct in choline oxidase.
  Biochemistry, 48, 720-728.  
18582059 A.Mukherjee, V.V.Smirnov, M.P.Lanci, D.E.Brown, E.M.Shepard, D.M.Dooley, and J.P.Roth (2008).
Inner-sphere mechanism for molecular oxygen reduction catalyzed by copper amine oxidases.
  J Am Chem Soc, 130, 9459-9473.  
19053231 E.M.Shepard, K.M.Okonski, and D.M.Dooley (2008).
Kinetics and spectroscopic evidence that the Cu(I)-semiquinone intermediate reduces molecular oxygen in the oxidative half-reaction of Arthrobacter globiformis amine oxidase.
  Biochemistry, 47, 13907-13920.  
  19052360 P.Pirrat, M.A.Smith, A.R.Pearson, M.J.McPherson, and S.E.Phillips (2008).
Structure of a xenon derivative of Escherichia coli copper amine oxidase: confirmation of the proposed oxygen-entry pathway.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1105-1109.
PDB code: 2w0q
17401532 A.Holt, O.S.Degenhardt, P.D.Berry, J.S.Kapty, S.Mithani, D.J.Smith, and M.L.Di Paolo (2007).
The effects of buffer cations on interactions between mammalian copper-containing amine oxidases and their substrates.
  J Neural Transm, 114, 733-741.  
17207171 A.Madej, A.Reich, A.Orda, and J.C.Szepietowski (2007).
Vascular adhesion protein-1 (VAP-1) is overexpressed in psoriatic patients.
  J Eur Acad Dermatol Venereol, 21, 72-78.  
17409383 B.J.Johnson, J.Cohen, R.W.Welford, A.R.Pearson, K.Schulten, J.P.Klinman, and C.M.Wilmot (2007).
Exploring molecular oxygen pathways in Hansenula polymorpha copper-containing amine oxidase.
  J Biol Chem, 282, 17767-17776.
PDB codes: 2oov 2oqe
17186474 S.A.De Marothy, M.R.Blomberg, and P.E.Siegbahn (2007).
Elucidating the mechanism for the reduction of nitrite by copper nitrite reductase--a contribution from quantum chemical studies.
  J Comput Chem, 28, 528-539.  
16929109 A.P.Duff, A.E.Cohen, P.J.Ellis, K.Hilmer, D.B.Langley, D.M.Dooley, H.C.Freeman, and J.M.Guss (2006).
The 1.23 Angstrom structure of Pichia pastoris lysyl oxidase reveals a lysine-lysine cross-link.
  Acta Crystallogr D Biol Crystallogr, 62, 1073-1084.
PDB code: 1w7c
16924556 E.M.Shepard, and D.M.Dooley (2006).
Intramolecular electron transfer rate between active-site copper and TPQ in Arthrobacter globiformis amine oxidase.
  J Biol Inorg Chem, 11, 1039-1048.  
16791638 I.Bento, M.A.Carrondo, and P.F.Lindley (2006).
Reduction of dioxygen by enzymes containing copper.
  J Biol Inorg Chem, 11, 539-547.  
16777962 S.Eswaramoorthy, J.B.Bonanno, S.K.Burley, and S.Swaminathan (2006).
Mechanism of action of a flavin-containing monooxygenase.
  Proc Natl Acad Sci U S A, 103, 9832-9837.
PDB codes: 1vqw 2gv8 2gvc
16239734 E.Jakobsson, J.Nilsson, D.Ogg, and G.J.Kleywegt (2005).
Structure of human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1.
  Acta Crystallogr D Biol Crystallogr, 61, 1550-1562.
PDB codes: 2c10 2c11
  15743791 M.Merinen, H.Irjala, M.Salmi, I.Jaakkola, A.Hänninen, and S.Jalkanen (2005).
Vascular adhesion protein-1 is involved in both acute and chronic inflammation in the mouse.
  Am J Pathol, 166, 793-800.  
16218874 P.Chaudhuri, K.Wieghardt, T.Weyhermüller, T.K.Paine, S.Mukherjee, and C.Mukherjee (2005).
Biomimetic metal-radical reactivity: aerial oxidation of alcohols, amines, aminophenols and catechols catalyzed by transition metal complexes.
  Biol Chem, 386, 1023-1033.  
15954152 S.Kar, B.Sarkar, S.Ghumaan, D.Janardanan, J.van Slageren, J.Fiedler, V.G.Puranik, R.B.Sunoj, W.Kaim, and G.K.Lahiri (2005).
2,5-Dioxido-1,4-benzoquinonediimine (H2L2-), a hydrogen-bonding noninnocent bridging ligand related to aminated topaquinone: different oxidation state distributions in complexes [{(bpy)2Ru}2(mu-H2L)]n (n=0,+,2+,3+,4+) and [{(acac)2Ru}2(mu-H2L)]m (m=2-,-,0,+,2+).
  Chemistry, 11, 4901-4911.  
15843144 S.Longu, A.Padiglia, J.Z.Pedersen, A.Finazzi Agrò, A.Mura, P.Maccioni, G.Floris, and R.Medda (2005).
Nitric oxide covalently labels a 6-hydroxydopa-derived free radical intermediate in the catalytic cycle of copper/quinone-containing amine oxidase from lentil seedlings.
  Biol Chem, 386, 25-31.  
16046623 T.T.Airenne, Y.Nymalm, H.Kidron, D.J.Smith, M.Pihlavisto, M.Salmi, S.Jalkanen, M.S.Johnson, and T.A.Salminen (2005).
Crystal structure of the human vascular adhesion protein-1: unique structural features with functional implications.
  Protein Sci, 14, 1964-1974.
PDB codes: 1pu4 1us1
15259025 G.G.Yegutkin, T.Salminen, K.Koskinen, C.Kurtis, M.J.McPherson, S.Jalkanen, and M.Salmi (2004).
A peptide inhibitor of vascular adhesion protein-1 (VAP-1) blocks leukocyte-endothelium interactions under shear stress.
  Eur J Immunol, 34, 2276-2285.  
14690425 A.P.Duff, A.E.Cohen, P.J.Ellis, J.A.Kuchar, D.B.Langley, E.M.Shepard, D.M.Dooley, H.C.Freeman, and J.M.Guss (2003).
The crystal structure of Pichia pastoris lysyl oxidase.
  Biochemistry, 42, 15148-15157.
PDB code: 1n9e
15035803 F.Buffoni, and G.Ignesti (2003).
Biochemical aspects and functional role of the copper-containing amine oxidases.
  Inflammopharmacology, 11, 203-209.  
12926004 R.Prabhakar, and P.E.Siegbahn (2003).
A comparison of the mechanism for the reductive half-reaction between pea seedling and other copper amine oxidases (CAOs).
  J Comput Chem, 24, 1599-1609.  
12153561 E.M.Shepard, J.Smith, B.O.Elmore, J.A.Kuchar, L.M.Sayre, and D.M.Dooley (2002).
Towards the development of selective amine oxidase inhibitors. Mechanism-based inhibition of six copper containing amine oxidases.
  Eur J Biochem, 269, 3645-3658.  
12134140 M.Kim, T.Okajima, S.Kishishita, M.Yoshimura, A.Kawamori, K.Tanizawa, and H.Yamaguchi (2002).
X-ray snapshots of quinone cofactor biogenesis in bacterial copper amine oxidase.
  Nat Struct Biol, 9, 591-596.
PDB codes: 1ivu 1ivv 1ivw 1ivx
12186541 S.A.Mills, Y.Goto, Q.Su, J.Plastino, and J.P.Klinman (2002).
Mechanistic comparison of the cobalt-substituted and wild-type copper amine oxidase from Hansenula polymorpha.
  Biochemistry, 41, 10577-10584.  
11532005 A.Padiglia, R.Medda, A.Lorrai, M.Paci, J.Z.Pedersen, A.Boffi, A.Bellelli, A.F.Agrò, and G.Floris (2001).
Irreversible inhibition of pig kidney copper-containing amine oxidase by sodium and lithium ions.
  Eur J Biochem, 268, 4686-4697.  
11258907 B.Schwartz, A.K.Olgin, and J.P.Klinman (2001).
The role of copper in topa quinone biogenesis and catalysis, as probed by azide inhibition of a copper amine oxidase from yeast.
  Biochemistry, 40, 2954-2963.  
11729263 E.Díaz, A.Ferrández, M.A.Prieto, and J.L.García (2001).
Biodegradation of aromatic compounds by Escherichia coli.
  Microbiol Mol Biol Rev, 65, 523.  
11180321 M.A.Halcrow (2001).
Chemically Modified Amino Acids in Copper Proteins That Bind or Activate Dioxygen The author acknowledges the Royal Society (London) for a University Research Fellowship.
  Angew Chem Int Ed Engl, 40, 346-349.  
11290336 M.Salmi, G.G.Yegutkin, R.Lehvonen, K.Koskinen, T.Salminen, and S.Jalkanen (2001).
A cell surface amine oxidase directly controls lymphocyte migration.
  Immunity, 14, 265-276.  
  11274927 M.Salmi, and S.Jalkanen (2001).
VAP-1: an adhesin and an enzyme.
  Trends Immunol, 22, 211-216.  
11483492 S.Jalkanen, and M.Salmi (2001).
Cell surface monoamine oxidases: enzymes in search of a function.
  EMBO J, 20, 3893-3901.  
10998232 G.Ranghino, E.Scorza, T.Sjögren, P.A.Williams, M.Ricci, and J.Hajdu (2000).
Quantum mechanical interpretation of nitrite reduction by cytochrome cd1 nitrite reductase from Paracoccus pantotrophus.
  Biochemistry, 39, 10958-10966.  
11114510 H.Erlandsen, E.E.Abola, and R.C.Stevens (2000).
Combining structural genomics and enzymology: completing the picture in metabolic pathways and enzyme active sites.
  Curr Opin Struct Biol, 10, 719-730.  
11114513 I.Schlichting, and K.Chu (2000).
Trapping intermediates in the crystal: ligand binding to myoglobin.
  Curr Opin Struct Biol, 10, 744-752.  
10998254 L.A.Burzio, and J.H.Waite (2000).
Cross-linking in adhesive quinoproteins: studies with model decapeptides.
  Biochemistry, 39, 11147-11153.  
10903941 N.M.Okeley, and W.A.van der Donk (2000).
Novel cofactors via post-translational modifications of enzyme active sites.
  Chem Biol, 7, R159-R171.  
10933787 Z.Chen, B.Schwartz, N.K.Williams, R.Li, J.P.Klinman, and F.S.Mathews (2000).
Crystal structure at 2.5 A resolution of zinc-substituted copper amine oxidase of Hansenula polymorpha expressed in Escherichia coli.
  Biochemistry, 39, 9709-9717.
PDB code: 1ekm
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.