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PDBsum entry 2vz2

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
2vz2
Jmol
Contents
Protein chain
499 a.a. *
Ligands
FAD-MFG ×2
C15 ×2
Waters ×433
* Residue conservation analysis
PDB id:
2vz2
Name: Oxidoreductase
Title: Human mao b in complex with mofegiline
Structure: Amine oxidase [flavin-containing] b. Chain: a, b. Synonym: human monoamine oxidase b, mao-b, monoamine oxidase type b. Engineered: yes. Other_details: covalent bond between fad and mofegiline inhibitor
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: pichia pastoris. Expression_system_taxid: 4922
Resolution:
2.30Å     R-factor:   0.188     R-free:   0.229
Authors: D.Bonivento,A.Mattevi
Key ref: E.M.Milczek et al. (2008). Structural and mechanistic studies of mofegiline inhibition of recombinant human monoamine oxidase B. J Med Chem, 51, 8019-8026. PubMed id: 19053775
Date:
29-Jul-08     Release date:   16-Dec-08    
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    
 
 
J Med Chem 51:8019-8026 (2008)
PubMed id: 19053775  
 
 
Structural and mechanistic studies of mofegiline inhibition of recombinant human monoamine oxidase B.
E.M.Milczek, D.Bonivento, C.Binda, A.Mattevi, I.A.McDonald, D.E.Edmondson.
 
  ABSTRACT  
 
Mechanistic and structural studies have been carried out to investigate the molecular basis for the irreversible inhibition of human MAO-B by mofegiline. Competitive inhibition with substrate shows an apparent K(i) of 28 nM. Irreversible inhibition of MAO-B occurs with a 1:1 molar stoichiometry with no observable catalytic turnover. The absorption spectral properties of mofegiline inhibited MAO-B show features (lambda(max) approximately 450 nm) unlike those of traditional flavin N(5) or C(4a) adducts. Visible and near-UV circular dichroism spectra of the mofegiline-MAO-B adduct shows a negative peak at 340 nm with an intensity similar to that of N(5) flavocyanine adducts. The X-ray crystal structure of the mofegiline-MAO-B adduct shows a covalent bond between the flavin cofactor N(5) with the distal allylamine carbon atom as well as the absence of the fluorine atom. A mechanism to explain these structural and spectral data is proposed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
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.  
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