5X2L

Crystal Structure of Human Serine Racemase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.81 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.222 

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Ligand Structure Quality Assessment 


This is version 1.1 of the entry. See complete history


Literature

Design, synthesis, and evaluation of novel inhibitors for wild-type human serine racemase.

Takahara, S.Nakagawa, K.Uchiyama, T.Yoshida, T.Matsumoto, K.Kawasumi, Y.Mizuguchi, M.Obita, T.Watanabe, Y.Hayakawa, D.Gouda, H.Mori, H.Toyooka, N.

(2017) Bioorg Med Chem Lett 

  • DOI: https://doi.org/10.1016/j.bmcl.2017.12.021
  • Primary Citation of Related Structures:  
    5X2L

  • PubMed Abstract: 

    Most of the endogenous free d-serine (about 90%) in the brain is produced by serine racemase (SR). d-Serine in the brain is involved in neurodegenerative disorders and epileptic states as an endogenous co-agonist of the NMDA-type glutamate receptor. Thus, SR inhibitors are expected to be novel therapeutic candidates for the treatment of these disorders. In this study, we solved the crystal structure of wild-type SR, and tried to identify a new inhibitor of SR by in silico screening using the structural information. As a result, we identified two hit compounds by their in vitro evaluations using wild-type SR. Based on the structure of the more potent hit compound 1, we synthesized 15 derivatives and evaluated their inhibitory activities against wild-type SR. Among them, the compound 9C showed relatively high inhibitory potency for wild-type SR. Compound 9C was a more potent inhibitor than compound 24, which was synthesized by our group based upon the structural information of the mutant-type SR.


  • Organizational Affiliation

    Graduate School of Innovative Life Science, University of Toyama, Japan.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Serine racemase
A, B
348Homo sapiensMutation(s): 0 
Gene Names: SRR
EC: 5.1.1.18 (PDB Primary Data), 4.3.1.18 (PDB Primary Data), 4.3.1.17 (PDB Primary Data)
UniProt & NIH Common Fund Data Resources
Find proteins for Q9GZT4 (Homo sapiens)
Explore Q9GZT4 
Go to UniProtKB:  Q9GZT4
PHAROS:  Q9GZT4
GTEx:  ENSG00000167720 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9GZT4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.81 Å
  • R-Value Free: 0.258 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.222 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 80.12α = 90
b = 112.59β = 90
c = 88γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
iMOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2018-01-31
    Type: Initial release
  • Version 1.1: 2021-02-24
    Changes: Derived calculations