Structure of PDB 6n1t Chain B

Receptor sequence

>6n1tB (length=511) Species: 5811 (Toxoplasma gondii)

PVCLVVAMTPKRGIGINNGLPWPHLTTDFKHFSRVTKTTPASRFNAVVMG
RKTWESMPRKFRPLVDRLNIVVSSSLKEEDIAAEKPQAEGQQRVRVCASL
PAALSLLEEEYKDSVDQIFVVGGAGLYEAALSLGVASHLYITRVAREFPC
DVFFPAFPGDDILSNKATYRPIFISKTFSDNGVPYDFVVLEKRRSSAAAI
APVLAWMDEELIRAVPHVHFRGHEEFQYLDLIADIINNGRTMDDRTGVGV
ISKFGCTMRYSLDQAFPLLTTKRVFWKGVLEELLWFIRGDTNANHLSEKG
VKIWDKNVTREFLDSRNLPHREVGDIGPGYGFQWRHFGAAYKDMHTDYTG
QGVDQLKNVIQMLRTNPTDRRMLMTAWNPAALDEMALPPCHLLCQFYVND
QKELSCIMYQRSCDVGLGVPFNIASYSLLTLMVAHVCNLKPKEFIHFMGN
THVYTNHVEALKEQLRREPRPFPIVNILNKERIKEIDDFTAEDFEVVGYV
PHGRIQMEMAV

3D structure

• PDB: 6n1t Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis.
• Chain: B
• Resolution: 3.5 Å

Enzymatic activity

• Catalytic site (original residue number in PDB): L23 D31 E381 W403 Y429 C489 R510 D513
• Catalytic site (residue number reindexed from 1): L20 D28 E282 W304 Y330 C390 R411 D414
• Enzyme Commision number: 1.5.1.3: dihydrofolate reductase.
  2.1.1.45: thymidylate synthase.

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	UMP	B	R469 R470	R370 R371
BS02	UMP	B	R344 L486 C489 H490 Q509 R510 S511 D513 N521 H551	R245 L387 C390 H391 Q410 R411 S412 D414 N422 H452
BS03	NDP	B	V9 A10 I17 N21 G22 W25 R81 K82 T83 V102 S104 S129 V151 G153 A154 G155 L156 V182	V6 A7 I14 N18 G19 W22 R51 K52 T53 V72 S74 S99 V121 G123 A124 G125 L126 V152
BS04	BOD	B	V8 V9 L23 H27 D31 F32 F35 M87 P88 V151	V5 V6 L20 H24 D28 F29 F32 M57 P58 V121	BindingDB: IC50=1.6nM

Gene Ontology

Molecular Function

• GO:0004146 dihydrofolate reductase activity
• GO:0004799 thymidylate synthase activity
• GO:0008168 methyltransferase activity
• GO:0016491 oxidoreductase activity
• GO:0016741 transferase activity, transferring one-carbon groups

Biological Process

• GO:0006231 dTMP biosynthetic process
• GO:0006730 one-carbon metabolic process
• GO:0009165 nucleotide biosynthetic process
• GO:0032259 methylation
• GO:0046654 tetrahydrofolate biosynthetic process

Cellular Component

• GO:0005739 mitochondrion
• GO:0005829 cytosol

External links

• PDB: RCSB:6n1t, PDBe:6n1t, PDBj:6n1t
• PDBsum: 6n1t
• PubMed: 30624926
• UniProt: Q07422|DRTS_TOXGO Bifunctional dihydrofolate reductase-thymidylate synthase