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PDBsum entry 1s3b

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1s3b
Jmol
Contents
Protein chain
499 a.a. *
Ligands
FAD-RMA ×2
Waters ×819
* Residue conservation analysis
PDB id:
1s3b
Name: Oxidoreductase
Title: Crystal structure of maob in complex with n-methyl-n- propargyl-1(r)-aminoindan
Structure: Amine oxidase [flavin-containing] b. Chain: a, b. Synonym: monoamine oxidase, mao-b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: maob. Expressed in: pichia pastoris. Expression_system_taxid: 4922.
Biol. unit: Dimer (from PQS)
Resolution:
1.65Å     R-factor:   0.204     R-free:   0.223
Authors: C.Binda,F.Hubalek,M.Li,Y.Herzig,J.Sterling,D.E.Edmondson, A.Mattevi
Key ref: C.Binda et al. (2004). Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class. J Med Chem, 47, 1767-1774. PubMed id: 15027868 DOI: 10.1021/jm031087c
Date:
13-Jan-04     Release date:   30-Mar-04    
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/jm031087c J Med Chem 47:1767-1774 (2004)
PubMed id: 15027868  
 
 
Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class.
C.Binda, F.Hubálek, M.Li, Y.Herzig, J.Sterling, D.E.Edmondson, A.Mattevi.
 
  ABSTRACT  
 
Monoamine oxidase B (MAO B) is an outer mitochondrial membrane enzyme that catalyzes the oxidation of arylalkylamine neurotransmitters. The crystal structures of MAO B in complex with four of the N-propargylaminoindan class of MAO covalent inhibitors (rasagiline, N-propargyl-1(S)-aminoindan, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan) have been determined at a resolution of better than 2.1 A. Rasagiline, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan adopt essentially the same conformation with the extended propargyl chain covalently bound to the flavin and the indan ring located in the rear of the substrate cavity. N-Propargyl-1(S)-aminoindan binds with the indan ring in a flipped conformation with respect to the other inhibitors, which causes a slight movement of the Tyr326 side chain. Four ordered water molecules are an integral part of the active site and establish H-bond interactions to the inhibitor atoms. These structural studies may guide future drug design to improve selectivity and efficacy by introducing appropriate substituents on the rasagiline molecular scaffold.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20862720 D.Schwarzer (2010).
Chemical tools in chromatin research.
  J Pept Sci, 16, 530-537.  
20600573 O.Weinreb, T.Amit, O.Bar-Am, and M.B.Youdim (2010).
Rasagiline: a novel anti-Parkinsonian monoamine oxidase-B inhibitor with neuroprotective activity.
  Prog Neurobiol, 92, 330-344.  
19894083 S.Gal, Z.A.Abassi, and M.B.Youdim (2010).
limited potentiation of blood pressure in response to oral tyramine by the anti-Parkinson brain selective multifunctional monoamine oxidase-AB inhibitor, M30.
  Neurotox Res, 18, 143-150.  
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.  
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.  
18343668 F.Forneris, C.Binda, E.Battaglioli, and A.Mattevi (2008).
LSD1: oxidative chemistry for multifaceted functions in chromatin regulation.
  Trends Biochem Sci, 33, 181-189.  
18640844 S.Hruschka, T.C.Rosen, S.Yoshida, K.L.Kirk, R.Fröhlich, B.Wibbeling, and G.Haufe (2008).
Fluorinated phenylcyclopropylamines. Part 5: Effects of electron-withdrawing or -donating aryl substituents on the inhibition of monoamine oxidases A and B by 2-aryl-2-fluoro-cyclopropylamines.
  Bioorg Med Chem, 16, 7148-7166.  
18426222 T.A.White, W.H.Johnson, C.P.Whitman, and J.J.Tanner (2008).
Structural basis for the inactivation of Thermus thermophilus proline dehydrogenase by N-propargylglycine.
  Biochemistry, 47, 5573-5580.
PDB code: 2ekg
17401533 K.Yelekçi, O.Karahan, and M.Toprakçi (2007).
Docking of novel reversible monoamine oxidase-B inhibitors: efficient prediction of ligand binding sites and estimation of inhibitors thermodynamic properties.
  J Neural Transm, 114, 725-732.  
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.  
16552415 M.B.Youdim, D.Edmondson, and K.F.Tipton (2006).
The therapeutic potential of monoamine oxidase inhibitors.
  Nat Rev Neurosci, 7, 295-309.  
16724525 M.Gütschow, and M.Meusel (2006).
[Enzyme inhibitors in Parkinson treatment]
  Pharm Unserer Zeit, 35, 218-225.  
16442801 N.Vlok, S.F.Malan, N.Castagnoli, J.J.Bergh, and J.P.Petzer (2006).
Inhibition of monoamine oxidase B by analogues of the adenosine A2A receptor antagonist (E)-8-(3-chlorostyryl)caffeine (CSC).
  Bioorg Med Chem, 14, 3512-3521.  
16366596 C.Binda, F.Hubálek, M.Li, Y.Herzig, J.Sterling, D.E.Edmondson, and A.Mattevi (2005).
Binding of rasagiline-related inhibitors to human monoamine oxidases: a kinetic and crystallographic analysis.
  J Med Chem, 48, 8148-8154.
PDB codes: 2c64 2c65 2c66 2c67
15710600 F.Hubálek, C.Binda, A.Khalil, M.Li, A.Mattevi, N.Castagnoli, and D.E.Edmondson (2005).
Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors.
  J Biol Chem, 280, 15761-15766.
PDB codes: 2bk3 2bk4 2bk5
16181413 H.Zheng, S.Gal, L.M.Weiner, O.Bar-Am, A.Warshawsky, M.Fridkin, and M.B.Youdim (2005).
Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases: in vitro studies on antioxidant activity, prevention of lipid peroxide formation and monoamine oxidase inhibition.
  J Neurochem, 95, 68-78.  
16129825 L.De Colibus, M.Li, C.Binda, A.Lustig, D.E.Edmondson, and A.Mattevi (2005).
Three-dimensional structure of human monoamine oxidase A (MAO A): relation to the structures of rat MAO A and human MAO B.
  Proc Natl Acad Sci U S A, 102, 12684-12689.
PDB codes: 2bxr 2bxs 2byb
16275926 M.Nadella, M.A.Bianchet, S.B.Gabelli, J.Barrila, and L.M.Amzel (2005).
Structure and activity of the axon guidance protein MICAL.
  Proc Natl Acad Sci U S A, 102, 16830-16835.
PDB code: 2bra
16181414 S.Gal, H.Zheng, M.Fridkin, and M.B.Youdim (2005).
Novel multifunctional neuroprotective iron chelator-monoamine oxidase inhibitor drugs for neurodegenerative diseases. In vivo selective brain monoamine oxidase inhibition and prevention of MPTP-induced striatal dopamine depletion.
  J Neurochem, 95, 79-88.  
15300824 T.C.Rosen, S.Yoshida, K.L.Kirk, and G.Haufe (2004).
Fluorinated phenylcyclopropylamines as inhibitors of monoamine oxidases.
  Chembiochem, 5, 1033-1043.  
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.