PDBsum entry 6j3c

Oxidoreductase/oxidoreductase inhibitor

PDB id: 6j3c

Contents

Protein chain

363 a.a.

Ligands

SO4 ×4

FMN

ORO

B5X

LDA

Waters ×282

PDB id:

6j3c

Name:

Oxidoreductase/oxidoreductase inhibitor

Title:

Crystal structure of human dhodh in complex with inhibitor 1291

Structure:

Dihydroorotate dehydrogenase (quinone), mitochondrial. Chain: a. Synonym: dhodehase,dihydroorotate oxidase. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dhodh. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.85Å R-factor: 0.170 R-free: 0.195

Authors:

Y.Yu,Q.Chen

Key ref:

T.Zeng et al. (2019). A novel series of human dihydroorotate dehydrogenase inhibitors discovered by in vitro screening: inhibition activity and crystallographic binding mode. FEBS Open Bio, 9, 1348-1354. PubMed id: 31087527 DOI: 10.1002/2211-5463.12658

Date:

04-Jan-19 Release date: 21-Aug-19

Protein chain

Q02127  (PYRD_HUMAN) -  Dihydroorotate dehydrogenase (quinone), mitochondrial from Homo sapiens

Seq: 395 a.a.

Struc: 363 a.a.

Enzyme reactions

• Enzyme class: E.C.1.3.5.2 - dihydroorotate dehydrogenase (quinone).
• Reaction: (S)-dihydroorotate + a quinone = orotate + a quinol

(S)-dihydroorotate (Bound ligand (Het Group name = ORO) corresponds exactly) + quinone = orotate + quinol

• Cofactor: FMN

FMN (Bound ligand (Het Group name = FMN) corresponds exactly)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1002/2211-5463.12658

FEBS Open Bio 9:1348-1354 (2019)

PubMed id: 31087527

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

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

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.