Structure of PDB 4ky4 Chain H

Receptor sequence

>4ky4H (length=491) Species: 5811 (Toxoplasma gondii)

KPVCLVVAMTPKRGIGINNGLPWPHLTTDFKHFSRVTKTFNAVVMGRKTW
ESMPRKFRPLVDRLNIVVSSSLKVCASLPAALSLLEEEYKDSVDQIFVVG
AGLYEAALSLGVASHLYITRVAREFPCDVFFPAFPGDDILSNKEATYRPI
FISKTFSDNGVPYDFVVLEKRSSAAAIAPVLAWMDEEDKELIRAVPHVHF
RGHEEFQYLDLIADIINNGRTMDDRTGVGVISKFGCTMRYSLDQAFPLLT
TKRVFWKGVLEELLWFIRGDTNANHLSEKGVKIWDKNVTREFLDSRNLPH
REVGDIGPGYGFQWRHFGAAYKDMHTDYTGQGVDQLKNVIQMLRTNPTDR
RMLMTAWNPAALDEMALPPCHLLCQFYVNDQKELSCIMYQRSCDVGLGVP
FNIASYSLLTLMVAHVCNLKPKEFIHFMGNTHVYTNHVEALKEQLRREPR
PFPIVNILNKERIKEIDDFTAEDFEVVGYVPHGRIQMEMAV

3D structure

• PDB: 4ky4 Discovery of potent and selective inhibitors of Toxoplasma gondii thymidylate synthase for opportunistic infections.
• Chain: H
• Resolution: 2.79 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): L21 D29 E262 W284 Y310 C370 R391 D394
• 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	H	C489 H490 Q509 R510 S511 D513 N521 H551	C370 H371 Q390 R391 S392 D394 N402 H432
BS02	04J	H	V8 V9 A10 D31 F32 F35 S36 F91 L94 R97	V6 V7 A8 D29 F30 F33 S34 F57 L60 R63
BS03	NDP	H	A10 I17 N21 G22 G80 R81 K82 T83 V102 S103 G153 A154	A8 I15 N19 G20 G46 R47 K48 T49 V68 S69 G100 A101
BS04	1UE	H	I402 W403 D513 L516 G517 M608	I283 W284 D394 L397 G398 M489	BindingDB: IC50=23nM

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:4ky4, PDBe:4ky4, PDBj:4ky4
• PDBsum: 4ky4
• PubMed: 24470841
• UniProt: Q07422|DRTS_TOXGO Bifunctional dihydrofolate reductase-thymidylate synthase