Structure of PDB 5t0l Chain B

Receptor sequence

>5t0lB (length=510) Species: 5811 (Toxoplasma gondii)

PVCLVVAMTPKRGIGINNGLPWPHLTTDFKHFSRVTKTTPASRFNAVVMG
RKTWESMPRKFRPLVDRLNIVVSSSLKEEDIAAEKPQAEGQQRVRVCASL
PAALSLLEEEYKDSVDQIFVVGGAGLYEAALSLGVASHLYITRVAREFPC
DVFFPAFPGDDILSNKATYRPIFISKTFSDNGVPYDFVVLEKRRSSAAAI
APVLAWMDELIRAVPHVHFRGHEEFQYLDLIADIINNGRTMDDRTGVGVI
SKFGCTMRYSLDQAFPLLTTKRVFWKGVLEELLWFIRGDTNANHLSEKGV
KIWDKNVTREFLDSRNLPHREVGDIGPGYGFQWRHFGAAYKDMHTDYTGQ
GVDQLKNVIQMLRTNPTDRRMLMTAWNPAALDEMALPPCHLLCQFYVNDQ
KELSCIMYQRSCDVGLGVPFNIASYSLLTLMVAHVCNLKPKEFIHFMGNT
HVYTNHVEALKEQLRREPRPFPIVNILNKERIKEIDDFTAEDFEVVGYVP
HGRIQMEMAV

3D structure

• PDB: 5t0l Discovery of Potent and Selective Leads against Toxoplasma gondii Dihydrofolate Reductase via Structure-Based Design.
• Chain: B
• Resolution: 3.13 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 E281 W303 Y329 C389 R410 D413
• 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	R369 R370
BS02	UMP	B	R344 L486 C489 H490 Q509 R510 S511 D513 N521 H551 Y553	R244 L386 C389 H390 Q409 R410 S411 D413 N421 H451 Y453
BS03	NDP	B	V9 A10 I17 N21 G22 L23 W25 G80 R81 K82 T83 V102 S103 S104 S105 V151 G153 A154 G155 V182	V6 A7 I14 N18 G19 L20 W22 G50 R51 K52 T53 V72 S73 S74 S75 V121 G123 A124 G125 V152
BS04	73X	B	V8 V9 A10 D31 F35 P88 V151	V5 V6 A7 D28 F32 P58 V121	BindingDB: IC50=17nM

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:5t0l, PDBe:5t0l, PDBj:5t0l
• PDBsum: 5t0l
• PubMed: 27994750
• UniProt: Q07422|DRTS_TOXGO Bifunctional dihydrofolate reductase-thymidylate synthase