Structure of PDB 3um6 Chain A Binding Site BS04

Receptor Information

>3um6 Chain A (length=546) Species: 5833 (Plasmodium falciparum)

MMEQVCDVFDIYAICVCCKVESKNEGKKNEVFNNYTFRGLGNKGVLPWKC
NSLDMKYFCAVTTYVNESKYEKLKYKRCKYLNKEKKLQNVVVMGRTTWES
IPKKFKPLSNRINVILSRTLKKEDFDEDVYIINKVEDLIVLLGKLNYYKC
FIIGGSVVYQEFLEKKLIKKIYFTRINSTYECDVFFPEINENEYQIISVS
DVYTSNNTTLDFIIYKKTNNDDEEEDDFVYFNFNKEKEEKNKNSIHPNDF
QIYNSLKYKYHPEYQYLNIIYDIMMNGNKQSDRTGVGVLSKFGYIMKFDL
SQYFPLLTTKKLFLRGIIEELLWFIRGETNGNTLLNKNVRIWEANGTREF
LDNRKLFHREVNDLGPIYGFQWRHFGAEYTNMYDNYENKGVDQLKNIINL
IKNDPTSRRILLCAWNVKDLDQMALPPCHILCQFYVFDGKLSCIMYQRSC
DLGLGVPFNIASYSIFTHMIAQVCNLQPAQFIHVLGNAHVYNNHIDSLKI
QLNRIPYPFPTLKLNPDIKNIEDFTISDFTIQNYVHHEKISMDMAA

Ligand information

• Ligand ID: UMP
• InChI: InChI=1S/C9H13N2O8P/c12-5-3-8(11-2-1-7(13)10-9(11)14)19-6(5)4-18-20(15,16)17/h1-2,5-6,8,12H,3-4H2,(H,10,13,14)(H2,15,16,17)/t5-,6+,8+/m0/s1
• InChIKey: JSRLJPSBLDHEIO-SHYZEUOFSA-N
• SMILES:
  ACDLabs 12.01: O=P(O)(O)OCC2OC(N1C(=O)NC(=O)C=C1)CC2O
  CACTVS 3.370: O[CH]1C[CH](O[CH]1CO[P](O)(O)=O)N2C=CC(=O)NC2=O
  OpenEye OEToolkits 1.7.6: C1[C@@H]([C@H](O[C@H]1N2C=CC(=O)NC2=O)COP(=O)(O)O)O
  CACTVS 3.370: O[C@H]1C[C@@H](O[C@@H]1CO[P](O)(O)=O)N2C=CC(=O)NC2=O
  OpenEye OEToolkits 1.7.6: C1C(C(OC1N2C=CC(=O)NC2=O)COP(=O)(O)O)O
• Formula: C9 H13 N2 O8 P
• Name: 2'-DEOXYURIDINE 5'-MONOPHOSPHATE;
  DUMP
• ChEMBL: CHEMBL211312
• DrugBank: DB03800
• ZINC: ZINC000004228260
• PDB chain: 3um6 Chain B Residue 711

Receptor-Ligand Complex Structure

Structure summary

• PDB: 3um6 Combined Spatial Limitation around Residues 16 and 108 of Plasmodium falciparum Dihydrofolate Reductase Explains Resistance to Cycloguanil.
• Resolution: 2.65 Å
• Binding residue (original residue number in PDB): R470 R471
• Binding residue (residue number reindexed from 1): R408 R409
• Annotation score: 3

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 E320 W342 Y368 C428 R448 D451
• Enzyme Commision number: 1.5.1.3: dihydrofolate reductase.
  2.1.1.45: thymidylate synthase.

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