Structure of PDB 6a2k Chain B

Receptor sequence

>6a2kB (length=527) Species: 5833 (Plasmodium falciparum)

VCDVFDIYAICACCKVESNEVFNNYTFRGLGNKGVLPWKCNSLDMKYFCA
VTTYVNESKYEKLKYKRCKYLNKKKLQNVVVMGRTSWESIPKKFKPLSNR
INVILSRTLKKEDDVYIINKVEDLIVLLGKLNYYKCFIIGGSVVYQEFLE
KKLIKKIYFTRINSTYECDVFFPEINENEYQIISVSDVYTSNNTTLDFII
YKKTNDEEEDDFVYFNFNKEKNKNSIHPNDFQIYNSLKYKYHPEYQYLNI
IYDIMMNGNKQSDRTGVGVLSKFGYIMKFDLSQYFPLLTTKKLFLRGIIE
ELLWFIRGETNGNTLLNKNVRIWEANGTREFLDNRKLFHREVNDLGPIYG
FQWRHFGAEYTNMYDNYENKGVDQLKNIINLIKNDPTSRRILLCAWNVKD
LDQMALPPCHILCQFYVFDGKLSCIMYQRSCDLGLGVPFNIASYSIFTHM
IAQVCNLQPAQFIHVLGNAHVYNNHIDSLKIQLNRIPYPFPTLKLNPDIK
NIEDFTISDFTIQNYVHHEKISMDMAA

3D structure

• PDB: 6a2k Hybrid Inhibitors of Malarial Dihydrofolate Reductase with Dual Binding Modes That Can Forestall Resistance.
• Chain: B
• Resolution: 2.38 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): L36 D44 E301 W323 Y349 C409 R429 D432
• 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	R389 R390
BS02	9QO	B	I14 C15 A16 L46 D54 M55 F58 P113 I164	I10 C11 A12 L36 D44 M45 F48 P91 I139	MOAD: Ki=0.44nM
BS03	NAP	B	C15 A16 L40 G44 V45 R106 T107 S108 L127 S128 R129 N144 I164 G165 G166 S167 V168 V169 E172	C11 A12 L30 G34 V35 R84 T85 S86 L105 S106 R107 N119 I139 G140 G141 S142 V143 V144 E147
BS04	UMP	B	C490 H491 Q509 R510 S511 D513 G517 N521 H551 Y553	C409 H410 Q428 R429 S430 D432 G436 N440 H470 Y472

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:6a2k, PDBe:6a2k, PDBj:6a2k
• PDBsum: 6a2k
• PubMed: 30613332
• UniProt: A7UD81