2Z5Y

Crystal Structure of Human Monoamine Oxidase A (G110A) with Harmine


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.17 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Structure of human monoamine oxidase A at 2.2-A resolution: The control of opening the entry for substrates/inhibitors

Son, S.Y.Ma, J.Kondou, Y.Yoshimura, M.Yamashita, E.Tsukihara, T.

(2008) Proc Natl Acad Sci U S A 105: 5739-5744

  • DOI: https://doi.org/10.1073/pnas.0710626105
  • Primary Citation of Related Structures:  
    2Z5X, 2Z5Y

  • PubMed Abstract: 

    The mitochondrial outer membrane-anchored monoamine oxidase (MAO) is a biochemically important flavoenzyme that catalyzes the deamination of biogenic and xenobiotic amines. Its two subtypes, MAOA and MAOB, are linked to several psychiatric disorders and therefore are interesting targets for drug design. To understand the relationship between structure and function of this enzyme, we extended our previous low-resolution rat MAOA structure to the high-resolution wild-type and G110A mutant human MAOA structures at 2.2 and 2.17 A, respectively. The high-resolution MAOA structures are similar to those of rat MAOA and human MAOB, but different from the known structure of human MAOA [De Colibus L, et al. (2005) Proc Natl Acad Sci USA 102:12684-12689], specifically regarding residues 108-118 and 210-216, which surround the substrate/inhibitor cavity. The results confirm that the inhibitor selectivity of MAOA and MAOB is caused by the structural differences arising from Ile-335 in MAOA vs. Tyr-326 in MAOB. The structures exhibit a C-terminal transmembrane helix with clear electron density, as is also seen in rat MAOA. Mutations on one residue of loop 108-118, G110, which is far from the active center but close to the membrane surface, cause the solubilized enzyme to undergo a dramatic drop in activity, but have less effect when the enzyme is anchored in the membrane. These results suggest that the flexibility of loop 108-118, facilitated by anchoring the enzyme into the membrane, is essential for controlling substrate access to the active site. We report on the observation of the structure-function relationship between a transmembrane helical anchor and an extra-membrane domain.


  • Organizational Affiliation

    Laboratory of Protein Crystallography, Institute for Protein Research, Osaka University, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Amine oxidase [flavin-containing] A513Homo sapiensMutation(s): 1 
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
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  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
HRM BindingDB:  2Z5Y Ki: min: 5, max: 17 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.17 Å
  • R-Value Free: 0.244 
  • R-Value Work: 0.193 
  • R-Value Observed: 0.196 
  • Space Group: C 2 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 135.547α = 90
b = 217.364β = 90
c = 54.804γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-01
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-11-10
    Changes: Database references, Derived calculations, Structure summary
  • Version 1.3: 2023-11-01
    Changes: Data collection, Refinement description