Structure of PDB 6vnd Chain A

Receptor sequence

>6vndA (length=365) Species: 9606 (Homo sapiens) [Search protein sequence]

ATGDERFYAEHLMPTLQGLLDPESAHRLAVRFTSLGLLPRARFQDSDMLE
VRVLGHKFRNPVGIAAGFDKHGEAVDGLYKMGFGFVEIGSVTPKPQEGNP
RPRVFRLPEDQAVINRYGFNSHGLSVVEHRLRARQQKQAKLTEDGLPLGV
NLGKNKTSVDAAEDYAEGVRVLGPLADYLVVNVSSPNTAGLRSLQGKAEL
RRLLTKVLQERDGLRRVHRPAVLVKIAPDLTSQDKEDIASVVKELGIDGL
IVTNTTVSRPAGLQGALRSETGGLSGKPLRDLSTQTIREMYALTQGRVPI
IGVGGVSSGQDALEKIRAGASLVQLYTALTFWGPPVVGKVKRELEALLKE
QGFGGVTDAIGADHR

3D structure

PDB

6vnd Selective Vulnerability to Pyrimidine Starvation in Hematologic Malignancies Revealed by AG-636, a Novel Clinical-Stage Inhibitor of Dihydroorotate Dehydrogenase.

Chain

Resolution

1.97 Å

3D
structure

Catalytic site residues are labeled in the structure
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Enzymatic activity

Catalytic site (original residue number in PDB)	N144 F148 S214 N216 T217 K254 N283
Catalytic site (residue number reindexed from 1)	N115 F119 S185 N187 T188 K225 N254
Enzyme Commision number	1.3.5.2: dihydroorotate dehydrogenase (quinone).

Interaction with ligand

Site #	Ligand	Ligand chain	Binding residues on receptor (original residue number in PDB)	Binding residues on receptor (residue number reindexed from 1)	Binding affinity
BS01	R4P	A	M42 Q46 P51 A54 H55 A58 L67 R135 Y355 T359 P363	M13 Q17 P22 A25 H26 A29 L38 R106 Y326 T330 P334	MOAD: ic50=17nM
BS02	FMN	A	A95 G96 K99 S119 N144 N180 N211 K254 N283 T284 S304 G305 V332 G333 G334 L354 Y355 T356	A66 G67 K70 S90 N115 N151 N182 K225 N254 T255 S275 G276 V303 G304 G305 L325 Y326 T327

Gene Ontology

	Molecular Function
GO:0004151	dihydroorotase activity
GO:0004152	dihydroorotate dehydrogenase activity
GO:0005515	protein binding
GO:0016491	oxidoreductase activity
GO:0016627	oxidoreductase activity, acting on the CH-CH group of donors
GO:0106430	dihydroorotate dehydrogenase (quinone) activity

	Biological Process
GO:0006207	'de novo' pyrimidine nucleobase biosynthetic process
GO:0006221	pyrimidine nucleotide biosynthetic process
GO:0006225	UDP biosynthetic process
GO:0009220	pyrimidine ribonucleotide biosynthetic process
GO:0044205	'de novo' UMP biosynthetic process

	Cellular Component
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005739	mitochondrion
GO:0005743	mitochondrial inner membrane
GO:0005829	cytosol
GO:0016020	membrane

View graph for
Molecular Function

View graph for
Biological Process

View graph for
Cellular Component

External links

PDB	RCSB:6vnd, PDBe:6vnd, PDBj:6vnd
PDBsum	6vnd
PubMed	33082276
UniProt	Q02127\|PYRD_HUMAN Dihydroorotate dehydrogenase (quinone), mitochondrial (Gene Name=DHODH)

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