Structure of PDB 6tvx Chain A Binding Site BS03

Receptor Information

>6tvx Chain A (length=517) Species: 9606 (Homo sapiens)

MWELTILHTNDVHSRLEQTSEDSSKCVDASRCMGGVARLFTKVQQIRRAE
PNVLLLDAGDQYQGTIWFTVYKGAEVAHFMNALRYDAMALGNHEFDNGVE
GLIEPLLKEAKFPILSANIKAKGPLASQISGLYLPYKVLPVGDEVVGIVG
YTSKETPFLSNPGTNLVFEDEITALQPEVDKLKTLNVNKIIALGHSGFEM
DKLIAQKVRGVDVVVGGHSNTFLYTGNPPSKEVPAGKYPFIVTSDDGRKV
PVVQAYAFGKYLGYLKIEFDERGNVISSHGNPILLDSSIPEDPSIKADIN
KWRIKLDDYSTQELGKTIVYLDGSSQSCRFRECNMGNLICDAMINNNLHV
SMCILNGGGIRSPIDERNDGTITWENLAAVLPFGGTFDLVQLKGSTLKKA
FEHSVHRYGQSTGEFLQVGGIHVVYDLSRKPGDRVVKLDVLCTKCRVPSY
DPLKMDEVYKVILPNFLANGGDGFQMIKDELLRHDSGDQDINVVSTYISK
MKVIYPAVEGRIKFSLE

Ligand information

• Ligand ID: NYW
• InChI: InChI=1S/C11H18N6O9P2/c12-8-5-9(16-11(13)15-8)17(2-14-5)10-7(19)6(18)4(26-10)1-25-28(23,24)3-27(20,21)22/h2,4,6-7,10,18-19H,1,3H2,(H,23,24)(H2,20,21,22)(H4,12,13,15,16)/t4-,6-,7-,10-/m1/s1
• InChIKey: YUBQMXICWXUXRX-KQYNXXCUSA-N
• SMILES:
  OpenEye OEToolkits 2.0.7: c1nc2c(nc(nc2n1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(CP(=O)(O)O)O)O)O)N)N
  CACTVS 3.385: Nc1nc(N)c2ncn([C@@H]3O[C@H](CO[P](O)(=O)C[P](O)(O)=O)[C@@H](O)[C@H]3O)c2n1
  OpenEye OEToolkits 2.0.7: c1nc2c(nc(nc2n1C3C(C(C(O3)COP(=O)(CP(=O)(O)O)O)O)O)N)N
  CACTVS 3.385: Nc1nc(N)c2ncn([CH]3O[CH](CO[P](O)(=O)C[P](O)(O)=O)[CH](O)[CH]3O)c2n1
• Formula: C11 H18 N6 O9 P2
• Name: [[(2~{R},3~{S},4~{R},5~{R})-5-[2,6-bis(azanyl)purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]methylphosphonic acid
• ChEMBL: CHEMBL4462911
• PDB chain: 6tvx Chain A Residue 603

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6tvx 2-Substituted alpha , beta-Methylene-ADP Derivatives: Potent Competitive Ecto-5'-nucleotidase (CD73) Inhibitors with Variable Binding Modes.
• Resolution: 2.6 Å
• Binding residue (original residue number in PDB): H38 D85 N117 H118 H243 N390 G392 R395 F417 G447 F500 D506
• Binding residue (residue number reindexed from 1): H13 D60 N92 H93 H218 N356 G358 R361 F383 G413 F466 D472
• Annotation score: 1
• Binding affinity: BindingDB: Ki=36nM

Enzymatic activity

• Catalytic site (original residue number in PDB): D36 H38 D85 N117 H118 D121 H220 H243 N245 S350 R354 R395
• Catalytic site (residue number reindexed from 1): D11 H13 D60 N92 H93 D96 H195 H218 N220 S325 R329 R361
• Enzyme Commision number: 3.1.3.35: thymidylate 5'-phosphatase.
  3.1.3.5: 5'-nucleotidase.
  3.1.3.89: 5'-deoxynucleotidase.
  3.1.3.91: 7-methylguanosine nucleotidase.
  3.1.3.99: IMP-specific 5'-nucleotidase.

Gene Ontology

Molecular Function

• GO:0000166 nucleotide binding
• GO:0002953 5'-deoxynucleotidase activity
• GO:0005515 protein binding
• GO:0008252 nucleotidase activity
• GO:0008253 5'-nucleotidase activity
• GO:0008270 zinc ion binding
• GO:0016787 hydrolase activity
• GO:0016788 hydrolase activity, acting on ester bonds
• GO:0042802 identical protein binding
• GO:0046872 metal ion binding
• GO:0050340 thymidylate 5'-phosphatase activity
• GO:0050483 IMP 5'-nucleotidase activity
• GO:0050484 GMP 5'-nucleotidase activity
• GO:0106411 XMP 5'-nucleosidase activity

Biological Process

• GO:0006196 AMP catabolic process
• GO:0006259 DNA metabolic process
• GO:0007159 leukocyte cell-cell adhesion
• GO:0009166 nucleotide catabolic process
• GO:0033198 response to ATP
• GO:0046032 ADP catabolic process
• GO:0046034 ATP metabolic process
• GO:0046086 adenosine biosynthetic process
• GO:0050728 negative regulation of inflammatory response
• GO:0055074 calcium ion homeostasis
• GO:0140928 inhibition of non-skeletal tissue mineralization

Cellular Component

• GO:0005654 nucleoplasm
• GO:0005829 cytosol
• GO:0005886 plasma membrane
• GO:0009897 external side of plasma membrane
• GO:0009986 cell surface
• GO:0016020 membrane
• GO:0070062 extracellular exosome
• GO:0098552 side of membrane

External links

• PDB: RCSB:6tvx, PDBe:6tvx, PDBj:6tvx
• PDBsum: 6tvx
• PubMed: 32045236
• UniProt: P21589|5NTD_HUMAN 5'-nucleotidase (Gene Name=NT5E)