Structure of PDB 6kot Chain B

Receptor sequence

>6kotB (length=522) Species: 5833 (Plasmodium falciparum)

QVCDVFDIYAICACCKVESNEVFNNYTFRGLGNKGVLPWKCISLDMKYFR
AVTTYVNESKYEKLKYKRCKYLNKKLQNVVVMGRTNWESIPKKFKPLSNR
INVILSRTLKKDEDVYIINKVEDLIVLLGKLNYYKCFILGGSVVYQEFLE
KKLIKKIYFTRINSTYECDVFFPEINENEYQIISVSDVYTSNNTTLDFII
YKKTNNDDEEEDDFVYFNFNKNSIHPNDFQIYNSLKYKYHPEYQYLNIIY
DIMMNGNKQSDRTGVGVLSKFGYIMKFDLSQYFPLLTTKKLFLRGIIEEL
LWFIRGETNGNTLLNKNVRIWEANGTREFLDNRKLFHREVNDLGPIYGFQ
WRHFGAEYTNMYDNYENKGVDQLKNIINLIKNDPTSRRILLCAWNVKDLD
QMALPPCHILCQFYVFDGKLSCIMYQRSCDLGLGVPFNIASYSIFTHMIA
QVCNLQPAQFIHVLGNAHVYNNHIDSLKIQLNRIPYPFPTLKLNPDIKNI
EDFTISDFTIQNYVHHEKISMD

3D structure

• PDB: 6kot 6-Hydrophobic aromatic substituent pyrimethamine analogues as potential antimalarials for pyrimethamine-resistant Plasmodium falciparum.
• Chain: B
• Resolution: 2.149 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 E299 W321 Y347 C407 R427 D430
• 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	R387 R388
BS02	DQ0	B	I14 C15 L46 D54 F58 N108 F116 R122	I11 C12 L37 D45 F49 N86 F94 R100	MOAD: Ki=4.96nM
BS03	NDP	B	C15 A16 L40 G44 V45 G105 R106 T107 N108 L127 S128 R129 T130 N144 L164 G166 S167 V168 V169 E172 V195	C12 A13 L31 G35 V36 G83 R84 T85 N86 L105 S106 R107 T108 N119 L139 G141 S142 V143 V144 E147 V170
BS04	UMP	B	R345 C490 H491 Q509 R510 S511 D513 N521 H551 Y553	R262 C407 H408 Q426 R427 S428 D430 N438 H468 Y470

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:6kot, PDBe:6kot, PDBj:6kot
• PDBsum: 6kot
• PubMed: 31685330
• UniProt: D9N170