2VZ2

Human MAO B in complex with mofegiline


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.188 

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This is version 1.4 of the entry. See complete history


Literature

Structural and mechanistic studies of mofegiline inhibition of recombinant human monoamine oxidase B.

Milczek, E.M.Bonivento, D.Binda, C.Mattevi, A.McDonald, I.A.Edmondson, D.E.

(2008) J Med Chem 51: 8019-8026

  • DOI: https://doi.org/10.1021/jm8011867
  • Primary Citation of Related Structures:  
    2VZ2

  • PubMed 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.


  • Organizational Affiliation

    Department of Chemistry, Emory University, 1510 Clifton Road, Atlanta, Georgia 30322, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
AMINE OXIDASE [FLAVIN-CONTAINING] B
A, B
520Homo sapiensMutation(s): 0 
EC: 1.4.3.4
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P27338 (Homo sapiens)
Explore P27338 
Go to UniProtKB:  P27338
PHAROS:  P27338
GTEx:  ENSG00000069535 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP27338
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.229 
  • R-Value Work: 0.187 
  • R-Value Observed: 0.188 
  • Space Group: C 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 132.026α = 90
b = 223.73β = 90
c = 86.629γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
CCP4phasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-12-16
    Type: Initial release
  • Version 1.1: 2011-05-07
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-02-28
    Changes: Database references, Structure summary
  • Version 1.4: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description