Structure of PDB 6z9b Chain A Binding Site BS04

Receptor Information

>6z9b Chain A (length=521) Species: 9606 (Homo sapiens)

MWELTILHTNDVHSRLEQTSEDSSKCVDASRCMGGVARLFTKVQQIRRAE
PNVLLLDAGDQYQGTIWFTVYKGAEVAHFMNALRYDAMALGNHEFDNGVE
GLIEPLLKEAKFPILSANIKAKGPLASQISGLYLPYKVLPVGDEVVGIVG
YTSKETPFLSNPGTNLVFEDEITALQPEVDKLKTLNVNKIIALGHSGFEM
DKLIAQKVRGVDVVVGGHSNTFLYTGNPPSKEVPAGKYPFIVTSDDGRKV
PVVQAYAFGKYLGYLKIEFDERGNVISSHGNPILLDSSIPEDPSIKADIN
KWRIKLDDYSTQELGKTIVYLDGSSQSCRFRECNMGNLICDAMINNNLRH
AFWNHVSMCILNGGGIRSPIDERNDGTITWENLAAVLPFGGTFDLVQLKG
STLKKAFEHSVHRYGQSTGEFLQVGGIHVVYDLSRKPGDRVVKLDVLCTK
CRVPSYDPLKMDEVYKVILPNFLANGGDGFQMIKDELLRHDSGDQDINVV
STYISKMKVIYPAVEGRIKFS

Ligand information

• Ligand ID: QCQ
• InChI: InChI=1S/C18H21ClFN5O8P2/c19-18-23-15(21-6-10-4-2-1-3-5-10)13-16(24-18)25(8-22-13)17-12(20)14(26)11(33-17)7-32-35(30,31)9-34(27,28)29/h1-5,8,11-12,14,17,26H,6-7,9H2,(H,30,31)(H,21,23,24)(H2,27,28,29)/t11-,12+,14-,17-/m1/s1
• InChIKey: PPWDVNAHTXSWKW-DMVWFOPNSA-N
• SMILES:
  OpenEye OEToolkits 2.0.7: c1ccc(cc1)CNc2c3c(nc(n2)Cl)n(cn3)C4C(C(C(O4)COP(=O)(CP(=O)(O)O)O)O)F
  OpenEye OEToolkits 2.0.7: c1ccc(cc1)CNc2c3c(nc(n2)Cl)n(cn3)[C@H]4[C@H]([C@@H]([C@H](O4)COP(=O)(CP(=O)(O)O)O)O)F
  CACTVS 3.385: O[C@H]1[C@H](F)[C@@H](O[C@@H]1CO[P](O)(=O)C[P](O)(O)=O)n2cnc3c(NCc4ccccc4)nc(Cl)nc23
  CACTVS 3.385: O[CH]1[CH](F)[CH](O[CH]1CO[P](O)(=O)C[P](O)(O)=O)n2cnc3c(NCc4ccccc4)nc(Cl)nc23
• Formula: C18 H21 Cl F N5 O8 P2
• Name: [[(2~{R},3~{R},4~{S},5~{R})-5-[2-chloranyl-6-[(phenylmethyl)amino]purin-9-yl]-4-fluoranyl-3-oxidanyl-oxolan-2-yl]methoxy-oxidanyl-phosphoryl]methylphosphonic acid
• ChEMBL: CHEMBL4779616
• PDB chain: 6z9b Chain A Residue 604

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6z9b Discovery of AB680: A Potent and Selective Inhibitor of CD73.
• Resolution: 2.17 Å
• Binding residue (original residue number in PDB): D85 N117 H118 D121 L184 S185 H243 N245 R354 N390 G392 R395 F417 G447 F500 D506
• Binding residue (residue number reindexed from 1): D60 N92 H93 D96 L159 S160 H218 N220 R329 N362 G364 R367 F389 G419 F472 D478
• Annotation score: 1
• Binding affinity: MOAD: ic50=0.7nM

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 R367
• 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:6z9b, PDBe:6z9b, PDBj:6z9b
• PDBsum: 6z9b
• PubMed: 32614585
• UniProt: P21589|5NTD_HUMAN 5'-nucleotidase (Gene Name=NT5E)