PDBsum entry 2vrl

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Oxidoreductase PDB id
Protein chain
499 a.a. *
Waters ×288
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Structure of human mao b in complex with benzylhydrazine
Structure: Amine oxidase [flavin-containing] b. Chain: a, b. Synonym: monoamine oxidase type b, mao-b, monoamine oxidase b. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: pichia pastoris. Expression_system_taxid: 4922
2.40Å     R-factor:   0.187     R-free:   0.234
Authors: C.Binda,J.Wang,M.Li,F.Hubalek,A.Mattevi,D.E.Edmondson
Key ref: C.Binda et al. (2008). Structural and mechanistic studies of arylalkylhydrazine inhibition of human monoamine oxidases A and B. Biochemistry, 47, 5616-5625. PubMed id: 18426226 DOI: 10.1021/bi8002814
09-Apr-08     Release date:   22-Apr-08    
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Protein chains
No UniProt id for this chain
Struc: 499 a.a.
Key:    Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   7 terms 
  Biological process     small molecule metabolic process   16 terms 
  Biochemical function     electron carrier activity     5 terms  


DOI no: 10.1021/bi8002814 Biochemistry 47:5616-5625 (2008)
PubMed id: 18426226  
Structural and mechanistic studies of arylalkylhydrazine inhibition of human monoamine oxidases A and B.
C.Binda, J.Wang, M.Li, F.Hubalek, A.Mattevi, D.E.Edmondson.
The structure and mechanism of human monoamine oxidase B (MAO B) inhibition by hydrazines are investigated and compared with data on human monoamine oxidase A (MAO A). The inhibition properties of phenylethylhydrazine, benzylhydrazine, and phenylhydrazine are compared for both enzymes. Benzylhydrazine is bound more tightly to MAO B than to MAO A, and phenylhydrazine is bound weakly by either enzyme. Phenylethylhydrazine stoichiometrically reduces the covalent FAD moieties of MAO A and of MAO B. Molecular oxygen is required for the inhibition reactions, and the level of O2 consumption for phenylethylhydrazine is 6-7-fold higher with either MAO A or MAO B than for the corresponding reactions with benzylhydrazine or phenylhydrazine. Mass spectral analysis of either inhibited enzyme shows the major product is a single covalent addition of the hydrazine arylalkyl group, although lower levels of dialkylated species are detected. Absorption and mass spectral data of the inhibited enzymes show that the FAD is the major site of alkylation. The three-dimensional (2.3 A) structures of phenylethylhydrazine- and benzylhydrazine-inhibited MAO B show that alkylation occurs at the N(5) position on the re face of the covalent flavin with loss of the hydrazyl nitrogens. A mechanistic scheme is proposed to account for these data, which involves enzyme-catalyzed conversion of the hydrazine to the diazene. From literature data on the reactivities of diazenes, O2 then reacts with the bound diazene to form an alkyl radical, N2 and superoxide anion. The bound arylalkyl radical reacts with the N(5) of the flavin, while the dissociated diazene reacts nonspecifically with the enzyme through arylalkylradicals.

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.  
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.  
19053775 E.M.Milczek, D.Bonivento, C.Binda, A.Mattevi, I.A.McDonald, and D.E.Edmondson (2008).
Structural and mechanistic studies of mofegiline inhibition of recombinant human monoamine oxidase B.
  J Med Chem, 51, 8019-8026.
PDB code: 2vz2
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