3CUK

Crystal structure of human D-amino acid oxidase: bound to an inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.49 Å
  • R-Value Free: 0.329 
  • R-Value Work: 0.239 
  • R-Value Observed: 0.243 

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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors.

Sparey, T.Abeywickrema, P.Almond, S.Brandon, N.Byrne, N.Campbell, A.Hutson, P.H.Jacobson, M.Jones, B.Munshi, S.Pascarella, D.Pike, A.Prasad, G.S.Sachs, N.Sakatis, M.Sardana, V.Venkatraman, S.Young, M.B.

(2008) Bioorg Med Chem Lett 18: 3386-3391

  • DOI: https://doi.org/10.1016/j.bmcl.2008.04.020
  • Primary Citation of Related Structures:  
    3CUK

  • PubMed Abstract: 

    The 'NMDA hypofunction hypothesis of schizophrenia' can be tested in a number of ways. DAO is the enzyme primarily responsible for the metabolism of d-serine, a co-agonist for the NMDA receptor. We identified novel DAO inhibitors, in particular, acid 1, which demonstrated moderate potency for DAO in vitro and ex vivo, and raised plasma d-serine levels after dosing ip to rats. In parallel, analogues were prepared to survey the SARs of 1.


  • Organizational Affiliation

    Department of Medicinal Chemistry, Merck Sharp & Dohme, The Neuroscience Research Centre, Terlings Park, Harlow, Essex CM20 2QR, UK. tim_sparey@merck.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
D-amino-acid oxidase
A, B, C, D
347Homo sapiensMutation(s): 0 
Gene Names: DAODAMOX
EC: 1.4.3.3
UniProt & NIH Common Fund Data Resources
Find proteins for P14920 (Homo sapiens)
Explore P14920 
Go to UniProtKB:  P14920
PHAROS:  P14920
GTEx:  ENSG00000110887 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP14920
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
4P5 BindingDB:  3CUK Ki: 36 (nM) from 1 assay(s)
Kd: min: 3.1, max: 37 (nM) from 4 assay(s)
IC50: min: 9, max: 214 (nM) from 5 assay(s)
Binding MOAD:  3CUK IC50: 141 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.49 Å
  • R-Value Free: 0.329 
  • R-Value Work: 0.239 
  • R-Value Observed: 0.243 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 187.729α = 90
b = 51.145β = 110.45
c = 153.294γ = 90
Software Package:
Software NamePurpose
MOLREPphasing
REFMACrefinement
HKL-2000data 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: 2008-07-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2018-03-14
    Changes: Data collection
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description