Structure of PDB 6a2l Chain A

Receptor sequence

>6a2lA (length=529) Species: 5833 (Plasmodium falciparum)

MMEQVCDVFDIYAICACCKVESKKNEVFNNYTFRGLGNKGVLPWKCISLD
MKYFRAVTTYVNESKYEKLKYKRCKYLNKETKKLQNVVVMGRTNWESIPK
KFKPLSNRINVILSRTLKKEDFDEDVYIINKVEDLIVLLGKLNYYKCFIL
GGSVVYQEFLEKKLIKKIYFTRINSTYECDVFFPEINENEYQIISVSDVY
TSNNTTLDFIIYKKTNNDDEEEDDFVYFNFNKENDFQIYNSLKYKYHPEY
QYLNIIYDIMMNGNKQSDRTGVGVLSKFGYIMKFDLSQYFPLLTTKKLFL
RGIIEELLWFIRGETNGNTLLNKNVRIWEANGTREFLDNRKLFHREVNDL
GPIYGFQWRHFGAEYTNMYDNYENKGVDQLKNIINLIKNDPTSRRILLCA
WNVKDLDQMALPPCHILCQFYVFDGKLSCIMYQRSCDLGLGVPFNIASYS
IFTHMIAQVCNLQPAQFIHVLGNAHVYNNHIDSLKIQLNRIPYPFPTLKL
NPDIKNIEDFTISDFTIQNYVHHEKISMD

3D structure

• PDB: 6a2l Hybrid Inhibitors of Malarial Dihydrofolate Reductase with Dual Binding Modes That Can Forestall Resistance.
• Chain: A
• 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): L42 D50 E306 W328 Y354 C414 R434 D437
• 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	9QO	A	I14 C15 A16 L46 D54 M55 F58 P113 F116 L164	I14 C15 A16 L42 D50 M51 F54 P99 F102 L150	MOAD: Ki=2.32nM
BS02	NAP	A	C15 A16 L40 G44 V45 L46 G105 R106 T107 N108 L127 S128 R129 T130 N144 L164 G165 G166 S167 V168 V169 E172	C15 A16 L36 G40 V41 L42 G91 R92 T93 N94 L113 S114 R115 T116 N130 L150 G151 G152 S153 V154 V155 E158
BS03	UMP	A	R345 C490 H491 Q509 R510 S511 D513 N521 H551 Y553	R269 C414 H415 Q433 R434 S435 D437 N445 H475 Y477
BS04	UMP	A	R470 R471	R394 R395

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:6a2l, PDBe:6a2l, PDBj:6a2l
• PDBsum: 6a2l
• PubMed: 30613332
• UniProt: D9N170