Structure of PDB 6kpr Chain B

Receptor sequence

>6kprB (length=534) Species: 5833 (Plasmodium falciparum)

EQVCDVFDIYAICACCKVESEVFNNYTFRGLGNKGVLPWKCISLDMKYFR
AVTTYVNESKYEKLKYKRCKYLNKETVDSKKLQNVVVMGRTNWESIPKKF
KPLSNRINVILSRTLKKEDFDEDVYIINKVEDLIVLLGKLNYYKCFILGG
SVVYQEFLEKKLIKKIYFTRINSTYECDVFFPEINENEYQIISVSDVYTS
NNTTLDFIIYKKTNNDDEEEDDFVYFNFNKENKNSIHPNDFQIYNSLKYK
YHPEYQYLNIIYDIMMNGNKQSDRTGVGVLSKFGYIMKFDLSQYFPLLTT
KKLFLRGIIEELLWFIRGETNGNTLLNKNVRIWEANGTREFLDNRKLFHR
EVNDLGPIYGFQWRHFGAEYTNMYDNYENKGVDQLKNIINLIKNDPTSRR
ILLCAWNVKDLDQMALPPCHILCQFYVFDGKLSCIMYQRSCDLGLGVPFN
IASYSIFTHMIAQVCNLQPAQFIHVLGNAHVYNNHIDSLKIQLNRIPYPF
PTLKLNPDIKNIEDFTISDFTIQNYVHHEKISMD

3D structure

• PDB: 6kpr 6-Hydrophobic aromatic substituent pyrimethamine analogues as potential antimalarials for pyrimethamine-resistant Plasmodium falciparum.
• Chain: B
• Resolution: 2.1 Å

Enzymatic activity

• Catalytic site (original residue number in PDB): L46 D54 E382 W404 Y430 C490 R510 D513
• Catalytic site (residue number reindexed from 1): L37 D45 E311 W333 Y359 C419 R439 D442
• 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	R470 R471	R399 R400
BS02	UMP	B	R345 C490 H491 Q509 R510 S511 D513 N521 H551 Y553	R274 C419 H420 Q438 R439 S440 D442 N450 H480 Y482
BS03	NDP	B	C15 A16 L40 G44 V45 G105 R106 T107 N108 L127 S128 R129 T130 N144 K145 L164 G166 S167 V168 V169 E172 V195	C13 A14 L31 G35 V36 G89 R90 T91 N92 L111 S112 R113 T114 N128 K129 L148 G150 S151 V152 V153 E156 V179
BS04	DQF	B	I14 C15 V45 L46 D54 M55 F58 L164	I12 C13 V36 L37 D45 M46 F49 L148	MOAD: Ki=0.98nM

Gene Ontology

Molecular Function

• GO:0000166 nucleotide binding
• 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:6kpr, PDBe:6kpr, PDBj:6kpr
• PDBsum: 6kpr
• PubMed: 31685330
• UniProt: D9N170