Structure of PDB 6a2m Chain A

Receptor sequence

>6a2mA (length=537) Species: 5833 (Plasmodium falciparum)

MMEQVCDVFDIYAICACCKVESKNEGKKNEVFNNYTFRGLGNKGVLPWKC
NSLDMKYFCAVTTYVNESKYEKLKYKRCKYLNKETKLQNVVVMGRTSWES
IPKKFKPLSNRINVILSRTLKKEDFDEDVYIINKVEDLIVLLGKLNYYKC
FIIGGSVVYQEFLEKKLIKKIYFTRINSTYECDVFFPEINENEYQIISVS
DVYTSNNTTLDFIIYKKTNNDDEEEDDFVYFNFNKEKNSIHPNDFQIYNS
LKYKYHPEYQYLNIIYDIMMNGNKQSDRTGVGVLSKFGYIMKFDLSQYFP
LLTTKKLFLRGIIEELLWFIRGETNGNTLLNKNVRIWEANGTREFLDNRK
LFHREVNDLGPIYGFQWRHFGAEYTNMYDNYENKGVDQLKNIINLIKNDP
TSRRILLCAWNVKDLDQMALPPCHILCQFYVFDGKLSCIMYQRSCDLGLG
VPFNIASYSIFTHMIAQVCNLQPAQFIHVLGNAHVYNNHIDSLKIQLNRI
PYPFPTLKLNPDIKNIEDFTISDFTIQNYVHHEKISM

3D structure

• PDB: 6a2m Hybrid Inhibitors of Malarial Dihydrofolate Reductase with Dual Binding Modes That Can Forestall Resistance.
• Chain: A
• Resolution: 2.2 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): L46 D54 E315 W337 Y363 C423 R443 D446
• 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	9QR	A	I14 C15 A16 D54 M55 F58 P113 F116 I164	I14 C15 A16 D54 M55 F58 P102 F105 I153	MOAD: Ki=0.35nM
BS02	NAP	A	C15 A16 L40 G44 V45 G105 R106 T107 S108 L127 S128 R129 T130 N144 I164 G166 S167 V168 V169 E172	C15 A16 L40 G44 V45 G94 R95 T96 S97 L116 S117 R118 T119 N133 I153 G155 S156 V157 V158 E161
BS03	UMP	A	R345 C490 Q509 R510 S511 D513 N521 H551 Y553	R278 C423 Q442 R443 S444 D446 N454 H484 Y486
BS04	UMP	A	R470 R471	R403 R404

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:6a2m, PDBe:6a2m, PDBj:6a2m
• PDBsum: 6a2m
• PubMed: 30613332
• UniProt: A7UD81