Structure of PDB 6oju Chain A Binding Site BS02

Receptor Information

>6oju Chain A (length=285) Species: 9606 (Homo sapiens)

SELQYLGQIQHILRCGVRKDDRTGTGTLSVFGMQARYSLRDEFPLLTTKR
VFWKGVLEELLWFIKGSTNAKELSSKGVKIWDANGSRDFLDSLGFSTREE
GDLGPVYGFQWRHFGAEYRDMESDYSGQGVDQLQRVIDTIKTNPDDRRII
MCAWNPRDLPLMALPPCHALCQFYVVNSELSCQLYQRSGDMGLGVPFNIA
SYALLTYMIAHITGLKPGDFIHTLGDAHIYLNHIEPLKIQLQREPRPFPK
LRILRKVEKIDDFKAEDFQIEGYNPHPTIKMEMAV

Ligand information

• Ligand ID: D96
• InChI: InChI=1S/C19H19N5O6/c20-19-23-15-14(17(28)24-19)11(8-21-15)7-9-1-3-10(4-2-9)16(27)22-12(18(29)30)5-6-13(25)26/h1-4,8,12H,5-7H2,(H,22,27)(H,25,26)(H,29,30)(H4,20,21,23,24,28)/t12-/m1/s1
• InChIKey: VDHBMZRBPMTLGE-GFCCVEGCSA-N
• SMILES:
  CACTVS 3.385: NC1=Nc2[nH]cc(Cc3ccc(cc3)C(=O)N[CH](CCC(O)=O)C(O)=O)c2C(=O)N1
  ACDLabs 12.01: N=2c1ncc(c1C(NC=2N)=O)Cc3ccc(cc3)C(=O)NC(CCC(O)=O)C(O)=O
  OpenEye OEToolkits 2.0.7: c1cc(ccc1Cc2c[nH]c3c2C(=O)NC(=N3)N)C(=O)NC(CCC(=O)O)C(=O)O
  CACTVS 3.385: NC1=Nc2[nH]cc(Cc3ccc(cc3)C(=O)N[C@H](CCC(O)=O)C(O)=O)c2C(=O)N1
  OpenEye OEToolkits 2.0.7: c1cc(ccc1Cc2c[nH]c3c2C(=O)NC(=N3)N)C(=O)N[C@H](CCC(=O)O)C(=O)O
• Formula: C19 H19 N5 O6
• Name: N-{4-[(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)methyl]benzene-1-carbonyl}-D-glutamic acid
• PDB chain: 6oju Chain A Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6oju Understanding the structural basis of species selective, stereospecific inhibition for Cryptosporidium and human thymidylate synthase.
• Resolution: 2.884 Å
• Binding residue (original residue number in PDB): K77 F80 I108 W109 N112 L221 G222 P224 F225 M311
• Binding residue (residue number reindexed from 1): K49 F52 I80 W81 N84 L193 G194 P196 F197 M283
• Annotation score: 2

Enzymatic activity

• Catalytic site (original residue number in PDB): E87 W109 Y135 C195 R215 D218
• Catalytic site (residue number reindexed from 1): E59 W81 Y107 C167 R187 D190
• Enzyme Commision number: 2.1.1.45: thymidylate synthase.

Gene Ontology

Molecular Function

• GO:0000900 mRNA regulatory element binding translation repressor activity
• GO:0003729 mRNA binding
• GO:0004799 thymidylate synthase activity
• GO:0005542 folic acid binding
• GO:0008168 methyltransferase activity
• GO:0016741 transferase activity, transferring one-carbon groups
• GO:0042803 protein homodimerization activity
• GO:1901363 heterocyclic compound binding
• GO:1990825 sequence-specific mRNA binding

Biological Process

• GO:0006206 pyrimidine nucleobase metabolic process
• GO:0006231 dTMP biosynthetic process
• GO:0006235 dTTP biosynthetic process
• GO:0006417 regulation of translation
• GO:0007623 circadian rhythm
• GO:0009165 nucleotide biosynthetic process
• GO:0009410 response to xenobiotic stimulus
• GO:0009636 response to toxic substance
• GO:0014070 response to organic cyclic compound
• GO:0017148 negative regulation of translation
• GO:0019860 uracil metabolic process
• GO:0032259 methylation
• GO:0032570 response to progesterone
• GO:0033189 response to vitamin A
• GO:0034097 response to cytokine
• GO:0035999 tetrahydrofolate interconversion
• GO:0045471 response to ethanol
• GO:0046653 tetrahydrofolate metabolic process
• GO:0046683 response to organophosphorus
• GO:0048589 developmental growth
• GO:0051216 cartilage development
• GO:0051384 response to glucocorticoid
• GO:0051593 response to folic acid
• GO:0060574 intestinal epithelial cell maturation
• GO:0071897 DNA biosynthetic process
• GO:0097421 liver regeneration

Cellular Component

• GO:0005634 nucleus
• GO:0005737 cytoplasm
• GO:0005739 mitochondrion
• GO:0005743 mitochondrial inner membrane
• GO:0005759 mitochondrial matrix
• GO:0005829 cytosol

External links

• PDB: RCSB:6oju, PDBe:6oju, PDBj:6oju
• PDBsum: 6oju
• PubMed: 31172516
• UniProt: P04818|TYSY_HUMAN Thymidylate synthase (Gene Name=TYMS)