Structure of PDB 3um6 Chain B

Receptor sequence

>3um6B (length=544) Species: 5833 (Plasmodium falciparum)

QVCDVFDIYAICVCCKVESKNEGKKNEVFNNYTFRGLGNKGVLPWKCNSL
DMKYFCAVTTYVNESKYEKLKYKRCKYLNKETVKLQNVVVMGRTTWESIP
KKFKPLSNRINVILSRTLKKEDFDEDVYIINKVEDLIVLLGKLNYYKCFI
IGGSVVYQEFLEKKLIKKIYFTRINSTYECDVFFPEINENEYQIISVSDV
YTSNNTTLDFIIYKKTNNDDEEEDDFVYFNFNKEKEEKNKNSIHPNDFQI
YNSLKYKYHPEYQYLNIIYDIMMNGNKQSDRTGVGVLSKFGYIMKFDLSQ
YFPLLTTKKLFLRGIIEELLWFIRGETNGNTLLNKNVRIWEANGTREFLD
NRKLFHREVNDLGPIYGFQWRHFGAEYTNMYDNYENKGVDQLKNIINLIK
NDPTSRRILLCAWNVKDLDQMALPPCHILCQFYVFDGKLSCIMYQRSCDL
GLGVPFNIASYSIFTHMIAQVCNLQPAQFIHVLGNAHVYNNHIDSLKIQL
NRIPYPFPTLKLNPDIKNIEDFTISDFTIQNYVHHEKISMDMAA

3D structure

• PDB: 3um6 Combined Spatial Limitation around Residues 16 and 108 of Plasmodium falciparum Dihydrofolate Reductase Explains Resistance to Cycloguanil.
• Chain: B
• Resolution: 2.65 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): L43 D51 E318 W340 Y366 C426 R446 D449
• 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	R406 R407
BS02	1CY	B	I14 C15 V16 D54 F58 T108 I112 I164	I11 C12 V13 D51 F55 T95 I99 I151	BindingDB: Ki=1.5nM
BS03	NDP	B	C15 V16 L40 G44 V45 L46 G105 R106 T107 T108 L127 S128 R129 N144 I164 G165 G166 S167 V168 V169 Y170 E172	C12 V13 L37 G41 V42 L43 G92 R93 T94 T95 L114 S115 R116 N131 I151 G152 G153 S154 V155 V156 Y157 E159
BS04	UMP	B	R345 C490 H491 Q509 R510 S511 D513 N521 H551	R281 C426 H427 Q445 R446 S447 D449 N457 H487

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:3um6, PDBe:3um6, PDBj:3um6
• PDBsum: 3um6
• PubMed: 22526319
• UniProt: A7UD81