6J3C

Crystal structure of human DHODH in complex with inhibitor 1291

PDB DOI: https://doi.org/10.2210/pdb6J3C/pdb

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

Deposited: 2019-01-04 Released: 2019-08-21
Deposition Author(s): Yu, Y., Chen, Q.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 1.85 ?
R-Value Free: 0.195
R-Value Work: 0.169
R-Value Observed: 0.170

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.1 of the entry. See complete history.

Literature

A novel series of human dihydroorotate dehydrogenase inhibitors discovered by in vitro screening: inhibition activity and crystallographic binding mode.

Zeng, T., Zuo, Z., Luo, Y., Zhao, Y., Yu, Y., Chen, Q.

(2019) FEBS Open Bio 9: 1348-1354

PubMed: 31087527 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1002/2211-5463.12658
Primary Citation of Related Structures:
6J3B, 6J3C

PubMed Abstract:
Human dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the rate-limiting step in de?novo pyrimidine biosynthesis, is considered to be an attractive target for potential treatment of autoimmune disease and cancer. Here, we present a novel class of human DHODH inhibitors with high inhibitory potency. The high-resolution crystal structures of human DHODH complexed with various agents reveal the details of their interactions. Comparisons with the binding modes of teriflunomide and brequinar provide insights that may facilitate the development of new inhibitors targeting human DHODH.

Organizational Affiliation

Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China.

Macromolecule Content

Total Structure Weight: 41.36 kDa
Atom Count: 3,166
Modelled Residue Count: 363
Deposited Residue Count: 366
Unique protein chains: 1

Macromolecules

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(by identity cutoff) | 3D Structure

Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Dihydroorotate dehydrogenase (quinone), mitochondrial	A	366	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 F [auth A] MOL2 format, chain F [auth A] mmCIF format, chain F [auth A]	F [auth A]	FLAVIN MONONUCLEOTIDE C₁₇ H₂₁ N₄ O₉ P FVTCRASFADXXNN-SCRDCRAPSA-N		Interactions Focus chain F [auth A] Interactions & Density Focus chain F [auth A]
B5X Query on B5X Download Ideal Coordinates CCD File SDF format, chain H [auth A] MOL2 format, chain H [auth A] mmCIF format, chain H [auth A]	H [auth A]	(6R)-1-[4-[3-(dimethylamino)phenyl]-3,5-bis(fluoranyl)phenyl]-6-propan-2-yl-6,7-dihydro-5H-benzotriazol-4-one C₂₃ H₂₄ F₂ N₄ O XGSICBDUCCZAFB-OAHLLOKOSA-N		Interactions Focus chain H [auth A] Interactions & Density Focus chain H [auth A]
LDA Query on LDA Download Ideal Coordinates CCD File SDF format, chain I [auth A] MOL2 format, chain I [auth A] mmCIF format, chain I [auth A]	I [auth A]	LAURYL DIMETHYLAMINE-N-OXIDE C₁₄ H₃₁ N O SYELZBGXAIXKHU-UHFFFAOYSA-N		Interactions Focus chain I [auth A] Interactions & Density Focus chain I [auth A]
ORO Query on ORO Download Ideal Coordinates CCD File SDF format, chain G [auth A] MOL2 format, chain G [auth A] mmCIF format, chain G [auth A]	G [auth A]	OROTIC ACID C₅ H₄ N₂ O₄ PXQPEWDEAKTCGB-UHFFFAOYSA-N		Interactions Focus chain G [auth A] Interactions & Density Focus chain G [auth A]
SO4 Query on SO4 Download Ideal Coordinates CCD File SDF format, chain B [auth A] SDF format, chain C [auth A] SDF format, chain D [auth A] SDF format, chain E [auth A] MOL2 format, chain B [auth A] MOL2 format, chain C [auth A] MOL2 format, chain D [auth A] MOL2 format, chain E [auth A] mmCIF format, chain B [auth A] mmCIF format, chain C [auth A] mmCIF format, chain D [auth A] mmCIF format, chain E [auth A]	B [auth A], C [auth A], D [auth A], E [auth A]	SULFATE ION O₄ S QAOWNCQODCNURD-UHFFFAOYSA-L		Interactions Focus chain B [auth A] Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A] Interactions & Density Focus chain B [auth A] Focus chain C [auth A] Focus chain D [auth A] Focus chain E [auth A]