1S2Y

Crystal structure of MAOB in complex with N-propargyl-1(S)-aminoindan


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.12 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.205 

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This is version 1.2 of the entry. See complete history


Literature

Crystal Structures of Monoamine Oxidase B in Complex with Four Inhibitors of the N-Propargylaminoindan Class.

Binda, C.Li, M.Herzig, Y.Sterling, J.Edmondson, D.E.Mattevi, A.

(2004) J Med Chem 47: 1767-1774

  • DOI: https://doi.org/10.1021/jm031087c
  • Primary Citation of Related Structures:  
    1S2Q, 1S2Y, 1S3B, 1S3E

  • PubMed 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.


  • Organizational Affiliation

    Department of Genetics and Microbiology, University of Pavia, Via Abbiategrasso 207, Pavia, 27100 Italy.


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 
Gene Names: MAOB
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
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
RSA BindingDB:  1S2Y Ki: 1.27e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.12 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.204 
  • R-Value Observed: 0.205 
  • Space Group: C 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 130.898α = 90
b = 224.218β = 90
c = 86.039γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
CCP4data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-03-30
    Type: Initial release
  • Version 1.1: 2008-04-29
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance