PDBsum entry: 2vrm

Oxidoreductase

PDB id: 2vrm

Contents

Protein chains

499 a.a. *

Ligands

FAD-PYL ×2

Waters ×437

* Residue conservation analysis

PDB id:

2vrm

Name:

Oxidoreductase

Title:

Structure of human mao b in complex with phenyethylhydrazine

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

Resolution:

2.30Å R-factor: 0.201 R-free: 0.246

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

Date:

09-Apr-08 Release date: 22-Apr-08

Protein chains

P27338  (AOFB_HUMAN) -  Amine oxidase [flavin-containing] B

Seq: 520 a.a.

Struc: 499 a.a.

Enzyme reactions

• Enzyme class: E.C.1.4.3.4 - Monoamine oxidase.
• Reaction: RCH₂NHR' + H₂O + O₂ = RCHO + R'NH₂ + H₂O₂
• 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 

• Cellular component: membrane (6 terms)
• Biological process: oxidation reduction (11 terms)
• Biochemical function: electron carrier activity (5 terms)

reference

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.

ABSTRACT

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.