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PDBsum entry 2v61

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
2v61
Jmol
Contents
Protein chain
499 a.a. *
Ligands
FAD ×2
C18 ×2
Waters ×921
* Residue conservation analysis
PDB id:
2v61
Name: Oxidoreductase
Title: Structure of human mao b in complex with the selective inhibitor 7-(3-chlorobenzyloxy)-4-(methylamino)methyl- coumarin
Structure: Amine oxidase (flavin-containing) b. Chain: a, b. Synonym: monoamine oxidase type b, mao-b, monoamine oxidase. Engineered: yes
Source: Homo sapiens. Organism_taxid: 9606. Expressed in: pichia pastoris. Expression_system_taxid: 4922
Resolution:
1.70Å     R-factor:   0.173     R-free:   0.201
Authors: C.Binda,J.Wang,L.Pisani,C.Caccia,A.Carotti,P.Salvati, D.E.Edmondson,A.Mattevi
Key ref: C.Binda et al. (2007). Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. J Med Chem, 50, 5848-5852. PubMed id: 17915852 DOI: 10.1021/jm070677y
Date:
13-Jul-07     Release date:   16-Oct-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P27338  (AOFB_HUMAN) -  Amine oxidase [flavin-containing] B
Seq:
Struc:
 
Seq:
Struc:
520 a.a.
499 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.4.3.4  - Monoamine oxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RCH2NHR' + H2O + O2 = RCHO + R'NH2 + H2O2
RCH(2)NHR'
+ H(2)O
+ O(2)
= RCHO
+ R'NH(2)
+ H(2)O(2)
      Cofactor: FAD
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     membrane   6 terms 
  Biological process     small molecule metabolic process   14 terms 
  Biochemical function     electron carrier activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/jm070677y J Med Chem 50:5848-5852 (2007)
PubMed id: 17915852  
 
 
Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs.
C.Binda, J.Wang, L.Pisani, C.Caccia, A.Carotti, P.Salvati, D.E.Edmondson, A.Mattevi.
 
  ABSTRACT  
 
Structures of human monoamine oxidase B (MAO B) in complex with safinamide and two coumarin derivatives, all sharing a common benzyloxy substituent, were determined by X-ray crystallography. These compounds competitively inhibit MAO B with Ki values in the 0.1-0.5 microM range that are 30-700-fold lower than those observed with MAO A. The inhibitors bind noncovalently to MAO B, occupying both the entrance and the substrate cavities and showing a similarly oriented benzyloxy substituent.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21442758 A.Gaspar, F.Teixeira, E.Uriarte, N.Milhazes, A.Melo, M.N.Cordeiro, F.Ortuso, S.Alcaro, and F.Borges (2011).
Towards the discovery of a novel class of monoamine oxidase inhibitors: structure-property-activity and docking studies on chromone amides.
  ChemMedChem, 6, 628-632.  
21354322 M.Aldeco, B.K.Arslan, and D.E.Edmondson (2011).
Catalytic and inhibitor binding properties of zebrafish monoamine oxidase (zMAO): comparisons with human MAO A and MAO B.
  Comp Biochem Physiol B Biochem Mol Biol, 159, 78-83.  
20012114 E.Agostinelli, G.Tempera, N.Viceconte, S.Saccoccio, V.Battaglia, S.Grancara, A.Toninello, and R.Stevanato (2010).
Potential anticancer application of polyamine oxidation products formed by amine oxidase: a new therapeutic approach.
  Amino Acids, 38, 353-368.  
20522954 K.Ravikumar, and B.Sridhar (2010).
Two polymorphs of safinamide, a selective and reversible inhibitor of monoamine oxidase B.
  Acta Crystallogr C, 66, o317-o320.  
20700534 P.F.Gherardini, G.Ausiello, and M.Helmer-Citterich (2010).
Superpose3D: a local structural comparison program that allows for user-defined structure representations.
  PLoS One, 5, e11988.  
19371079 D.E.Edmondson, C.Binda, J.Wang, A.K.Upadhyay, and A.Mattevi (2009).
Molecular and mechanistic properties of the membrane-bound mitochondrial monoamine oxidases.
  Biochemistry, 48, 4220-4230.  
19342233 E.M.Van der Walt, E.M.Milczek, S.F.Malan, D.E.Edmondson, N.Castagnoli, J.J.Bergh, and J.P.Petzer (2009).
Inhibition of monoamine oxidase by (E)-styrylisatin analogues.
  Bioorg Med Chem Lett, 19, 2509-2513.  
19673610 M.Naoi, and W.Maruyama (2009).
Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson's disease.
  Expert Rev Neurother, 9, 1233-1250.  
18549347 M.Onofrj, L.Bonanni, and A.Thomas (2008).
An expert opinion on safinamide in Parkinson's disease.
  Expert Opin Investig Drugs, 17, 1115-1125.  
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.