2BXR

Human Monoamine Oxidase A in complex with Clorgyline, Crystal Form A


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.195 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Three-Dimensional Structure of Human Monoamine Oxidase a (Mao A): Relation to the Structures of Rat Mao a and Human Mao B

De Colibus, L.Li, M.Binda, C.Lustig, A.Edmondson, D.E.Mattevi, A.

(2005) Proc Natl Acad Sci U S A 102: 12864

  • DOI: https://doi.org/10.1073/pnas.0505975102
  • Primary Citation of Related Structures:  
    2BXR, 2BXS, 2BYB

  • PubMed Abstract: 

    The three-dimensional structure of recombinant human monoamine oxidase A (hMAO A) as its clorgyline-inhibited adduct is described. Although the chain-fold of hMAO A is similar to that of rat MAO A and human MAO B (hMAO B), hMAO A is unique in that it crystallizes as a monomer and exhibits the solution hydrodynamic behavior of a monomeric form rather than the dimeric form of hMAO B and rat MAO A. hMAO A's active site consists of a single hydrophobic cavity of approximately 550 A3, which is smaller than that determined from the structure of deprenyl-inhibited hMAO B (approximately 700 A3) but larger than that of rat MAO A (approximately 450 A3). An important component of the active site structure of hMAO A is the loop conformation of residues 210-216, which differs from that of hMAO B and rat MAO A. The origin of this structural alteration is suggested to result from long-range interactions in the monomeric form of the enzyme. In addition to serving as a basis for the development of hMAO A specific inhibitors, these data support the proposal that hMAO A involves a change from the dimeric to the monomeric form through a Glu-151 --> Lys mutation that is specific of hMAO A [Andrès, A. M., Soldevila, M., Navarro, A., Kidd, K. K., Oliva, B. & Bertranpetit, J. (2004) Hum. Genet. 115, 377-386]. These considerations put into question the use of MAO A from nonhuman sources in drug development for use in humans.


  • Organizational Affiliation

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


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
AMINE OXIDASE [FLAVIN-CONTAINING] A
A, B
527Homo sapiensMutation(s): 0 
EC: 1.4.3.4
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P21397 (Homo sapiens)
Explore P21397 
Go to UniProtKB:  P21397
PHAROS:  P21397
GTEx:  ENSG00000189221 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP21397
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
MLG BindingDB:  2BXR Ki: min: 12, max: 1200 (nM) from 5 assay(s)
IC50: min: 4.90e-3, max: 48 (nM) from 52 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.00 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.195 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 143.493α = 90
b = 109.599β = 95.18
c = 81.329γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-08-09
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 1.2: 2019-10-02
    Changes: Data collection, Derived calculations, Other
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Refinement description