3KVK

Crystal structure of human dihydroorotate dehydrogenase (DHODH) with amino-benzoic acid inhibitor 641 at 2.05A resolution


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.186 

Starting Model: experimental
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Ligand Structure Quality Assessment 


This is version 1.3 of the entry. See complete history


Literature

Discovery of novel inhibitors for DHODH via virtual screening and X-ray crystallographic structures.

McLean, L.R.Zhang, Y.Degnen, W.Peppard, J.Cabel, D.Zou, C.Tsay, J.T.Subramaniam, A.Vaz, R.J.Li, Y.

(2010) Bioorg Med Chem Lett 20: 1981-1984

  • DOI: https://doi.org/10.1016/j.bmcl.2010.01.115
  • Primary Citation of Related Structures:  
    3KVJ, 3KVK, 3KVL, 3KVM

  • PubMed Abstract: 

    Amino-benzoic acid derivatives 1-4 were found to be inhibitors for DHODH by virtual screening, biochemical, and X-ray crystallographic studies. X-ray structures showed that 1 and 2 bind to DHODH as predicted by virtual screening, but 3 and 4 were found to be structurally different from the corresponding compounds initially identified by virtual screening.


  • Organizational Affiliation

    Discovery Research, Sanofi-aventis, Bridgewater, NJ 08807, USA. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Dihydroorotate dehydrogenase, mitochondrial390Homo sapiensMutation(s): 0 
Gene Names: DHODH
EC: 1.3.5.2
UniProt & NIH Common Fund Data Resources
Find proteins for Q02127 (Homo sapiens)
Explore Q02127 
Go to UniProtKB:  Q02127
PHAROS:  Q02127
GTEx:  ENSG00000102967 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ02127
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 5 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
FMN
Query on FMN

Download Ideal Coordinates CCD File 
C [auth A]FLAVIN MONONUCLEOTIDE
C17 H21 N4 O9 P
FVTCRASFADXXNN-SCRDCRAPSA-N
6X1
Query on 6X1

Download Ideal Coordinates CCD File 
F [auth A]2-{[(3,5-dichlorophenyl)carbamoyl]amino}benzoic acid
C14 H10 Cl2 N2 O3
PIWYMPXOKMFVER-UHFFFAOYSA-N
DET
Query on DET

Download Ideal Coordinates CCD File 
E [auth A]UNDECYLAMINE-N,N-DIMETHYL-N-OXIDE
C13 H29 N O
OZHBUVQCJMARBN-UHFFFAOYSA-N
DOR
Query on DOR

Download Ideal Coordinates CCD File 
D [auth A](4S)-2,6-DIOXOHEXAHYDROPYRIMIDINE-4-CARBOXYLIC ACID
C5 H6 N2 O4
UFIVEPVSAGBUSI-REOHCLBHSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A]SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
6X1 BindingDB:  3KVK IC50: 700 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.186 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 90.908α = 90
b = 90.908β = 90
c = 123.077γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
CNSrefinement
PDB_EXTRACTdata extraction
CNXrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2010-03-02
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-11-01
    Changes: Refinement description
  • Version 1.3: 2023-09-06
    Changes: Data collection, Database references, Derived calculations, Refinement description