3KVK

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

PDB DOI: https://doi.org/10.2210/pdb3KVK/pdb

Classification: OXIDOREDUCTASE
Organism(s): Homo sapiens
Expression System: Escherichia coli
Mutation(s): No

Deposited: 2009-11-30 Released: 2010-03-02
Deposition Author(s): McLean, L., Zhang, Y.

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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wwPDB Validation 3D Report Full Report

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

PubMed: 20153645 Search on PubMed
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]

Macromolecule Content

Total Structure Weight: 43.89 kDa
Atom Count: 3,105
Modelled Residue Count: 364
Deposited Residue Count: 390
Unique protein chains: 1

Macromolecules

Find similar proteins by:

(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Dihydroorotate dehydrogenase, mitochondrial	A	390	Homo sapiens	Mutation(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 Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt Group	Q02127
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
FMN Query on FMN Download Ideal Coordinates CCD File SDF format, chain C [auth A] MOL2 format, chain C [auth A] mmCIF format, chain C [auth A]	C [auth A]	FLAVIN MONONUCLEOTIDE C₁₇ H₂₁ N₄ O₉ P FVTCRASFADXXNN-SCRDCRAPSA-N		Interactions Focus chain C [auth A] Interactions & Density Focus chain C [auth A]
6X1 Query on 6X1 Download Ideal Coordinates CCD File SDF format, chain F [auth A] MOL2 format, chain F [auth A] mmCIF format, chain F [auth A]	F [auth A]	2-{[(3,5-dichlorophenyl)carbamoyl]amino}benzoic acid C₁₄ H₁₀ Cl₂ N₂ O₃ PIWYMPXOKMFVER-UHFFFAOYSA-N		Interactions Focus chain F [auth A] Interactions & Density Focus chain F [auth A]
DET Query on DET Download Ideal Coordinates CCD File SDF format, chain E [auth A] MOL2 format, chain E [auth A] mmCIF format, chain E [auth A]	E [auth A]	UNDECYLAMINE-N,N-DIMETHYL-N-OXIDE C₁₃ H₂₉ N O OZHBUVQCJMARBN-UHFFFAOYSA-N		Interactions Focus chain E [auth A] Interactions & Density Focus chain E [auth A]
DOR Query on DOR Download Ideal Coordinates CCD File SDF format, chain D [auth A] MOL2 format, chain D [auth A] mmCIF format, chain D [auth A]	D [auth A]	(4S)-2,6-DIOXOHEXAHYDROPYRIMIDINE-4-CARBOXYLIC ACID C₅ H₆ N₂ O₄ UFIVEPVSAGBUSI-REOHCLBHSA-N		Interactions Focus chain D [auth A] Interactions & Density Focus chain D [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain B [auth A] MOL2 format, chain B [auth A] mmCIF format, chain B [auth A]	B [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain B [auth A] Interactions & Density Focus chain B [auth A]

Binding Affinity Annotations
ID	Source	Binding 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 = 90.908	α = 90
b = 90.908	β = 90
c = 123.077	γ = 120

Software Package:

Software Name	Purpose
DENZO	data reduction
SCALEPACK	data scaling
MOLREP	phasing
CNS	refinement
PDB_EXTRACT	data extraction
CNX	refinement

Structure Validation

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Ligand Structure Quality Assessment

Entry History

Deposition Data

Released Date: 2010-03-02

Deposition Author(s):

McLean, L.

Zhang, Y.

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