PDBsum entry 2vvl

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Oxidoreductase PDB id
Protein chains
(+ 2 more) 478 a.a. *
FAD ×8
EDO ×7
Waters ×807
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: The structure of mao-n-d3, a variant of monoamine oxidase from aspergillus niger.
Structure: Monoamine oxidase n. Chain: a, b, c, d, e, f, h. Synonym: monoamine oxidase, mao-n. Engineered: yes. Mutation: yes. Other_details: flavin adenine dinucleotide cofactor. Monoamine oxidase n. Chain: g. Synonym: monoamine oxidase, mao-n.
Source: Aspergillus niger. Organism_taxid: 5061. Expressed in: escherichia coli. Expression_system_taxid: 562.
2.45Å     R-factor:   0.185     R-free:   0.236
Authors: K.E.Atkin,S.Hart,J.P.Turkenburg,A.M.Brzozowski,G.J.Grogan
Key ref:
K.E.Atkin et al. (2008). The structure of monoamine oxidase from Aspergillus niger provides a molecular context for improvements in activity obtained by directed evolution. J Mol Biol, 384, 1218-1231. PubMed id: 18951902 DOI: 10.1016/j.jmb.2008.09.090
10-Jun-08     Release date:   04-Nov-08    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P46882  (AOFN_ASPNG) -  Monoamine oxidase N
495 a.a.
478 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Monoamine oxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RCH2NHR' + H2O + O2 = RCHO + R'NH2 + H2O2
+ H(2)O
+ O(2)
Bound ligand (Het Group name = EDO)
matches with 40.00% similarity
+ R'NH(2)
+ H(2)O(2)
      Cofactor: FAD
Bound ligand (Het Group name = FAD) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     peroxisome   1 term 
  Biological process     oxidation-reduction process   1 term 
  Biochemical function     oxidoreductase activity     1 term  


DOI no: 10.1016/j.jmb.2008.09.090 J Mol Biol 384:1218-1231 (2008)
PubMed id: 18951902  
The structure of monoamine oxidase from Aspergillus niger provides a molecular context for improvements in activity obtained by directed evolution.
K.E.Atkin, R.Reiss, V.Koehler, K.R.Bailey, S.Hart, J.P.Turkenburg, N.J.Turner, A.M.Brzozowski, G.Grogan.
Monoamine oxidase from Aspergillus niger (MAO-N) is a flavoenzyme that catalyses the oxidative deamination of primary amines. MAO-N has been used as the starting model for a series of directed evolution experiments, resulting in mutants of improved activity and broader substrate specificity, suitable for application in the preparative deracemisation of primary, secondary and tertiary amines when used as part of a chemoenzymatic oxidation-reduction cycle. The structures of a three-point mutant (Asn336Ser/Met348Lys/Ile246Met or MAO-N-D3) and a five-point mutant (Asn336Ser/Met348Lys/Ile246Met/Thr384Asn/Asp385Ser or MAO-N-D5) have been obtained using a multiple-wavelength anomalous diffraction experiment on a selenomethionine derivative of the truncated MAO-N-D5 enzyme. MAO-N exists as a homotetramer with a large channel at its centre and shares some structural features with human MAO B (MAO-B). A hydrophobic cavity extends from the protein surface to the active site, where a non-covalently bound flavin adenine dinucleotide (FAD) sits at the base of an 'aromatic cage,' the sides of which are formed by Trp430 and Phe466. A molecule of l-proline was observed near the FAD, and this ligand superimposed well with isatin, a reversible inhibitor of MAO-B, when the structures of MAO-N proline and MAO-B-isatin were overlaid. Of the mutations that confer the ability to catalyse the oxidation of secondary amines in MAO-N-D3, Asn336Ser reduces steric bulk behind Trp430 of the aromatic cage and Ile246Met confers greater flexibility within the substrate binding site. The two additional mutations, Thr384Asn and Asp385Ser, that occur in the MAO-N-D5 variant, which is able to oxidise tertiary amines, appear to influence the active-site environment remotely through changes in tertiary structure that perturb the side chain of Phe382, again altering the steric and electronic character of the active site near FAD. The possible implications of the change in steric and electronic environment caused by relevant mutations are discussed with respect to the improved catalytic efficiency of the MAO-N variants described in the literature.
  Selected figure(s)  
Figure 1.
Fig. 1. Chemoenzymatic oxidation–reduction cycle for the deracemisation of racemic amines using MAO-N and abiotic reducing agents.
Figure 8.
Fig. 8. Wall-eyed stereoview of the location of the Ile246Met mutation in the hydrophobic cavity close to the ligand binding site. The structures of MAO-N-D3 (yellow) and MAO-N-D5 (green) are superimposed.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2008, 384, 1218-1231) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20480485 R.V.Dunn, A.W.Munro, N.J.Turner, S.E.Rigby, and N.S.Scrutton (2010).
Tyrosyl radical formation and propagation in flavin dependent monoamine oxidases.
  Chembiochem, 11, 1228-1231.  
20133612 S.Wu, J.P.Acevedo, and M.T.Reetz (2010).
Induced allostery in the directed evolution of an enantioselective Baeyer-Villiger monooxygenase.
  Proc Natl Acad Sci U S A, 107, 2775-2780.  
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.  
19692330 F.Sabbadin, R.Jackson, K.Haider, G.Tampi, J.P.Turkenburg, S.Hart, N.C.Bruce, and G.Grogan (2009).
The 1.5-A structure of XplA-heme, an unusual cytochrome P450 heme domain that catalyzes reductive biotransformation of royal demolition explosive.
  J Biol Chem, 284, 28467-28475.
PDB codes: 2wiv 2wiy
19620998 N.J.Turner (2009).
Directed evolution drives the next generation of biocatalysts.
  Nat Chem Biol, 5, 567-573.  
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.