Structure of PDB 6s7f Chain A Binding Site BS04

Receptor Information

>6s7f Chain A (length=519) Species: 9606 (Homo sapiens)

MWELTILHTNDVHSRLEQTSEDSSKCVDASRCMGGVARLFTKVQQIRRAE
PNVLLLDAGDQYQGTIWFTVYKGAEVAHFMNALRYDAMALGNHEFDNGVE
GLIEPLLKEAKFPILSANIKAKGPLASQISGLYLPYKVLPVGDEVVGIVG
YTSKETPFLSNPGTNLVFEDEITALQPEVDKLKTLNVNKIIALGHSGFEM
DKLIAQKVRGVDVVVGGHSNTFLYTGNPPSKEVPAGKYPFIVTSDDGRKV
PVVQAYAFGKYLGYLKIEFDERGNVISSHGNPILLDSSIPEDPSIKADIN
KWRIKLDDYSTQELGKTIVYLDGSSQSCRFRECNMGNLICDAMINNNLRN
HVSMCILNGGGIRSPIDERNDGTITWENLAAVLPFGGTFDLVQLKGSTLK
KAFEHSVHRYGQSTGEFLQVGGIHVVYDLSRKPGDRVVKLDVLCTKCRVP
SYDPLKMDEVYKVILPNFLANGGDGFQMIKDELLRHDSGDQDINVVSTYI
SKMKVIYPAVEGRIKFSLE

Ligand information

• Ligand ID: KYK
• InChI: InChI=1S/C18H23N5O9P2/c24-14-12(7-31-34(29,30)10-33(26,27)28)32-18(15(14)25)23-9-22-13-16(20-8-21-17(13)23)19-6-11-4-2-1-3-5-11/h1-5,8-9,12,14-15,18,24-25H,6-7,10H2,(H,29,30)(H,19,20,21)(H2,26,27,28)/t12-,14-,15-,18-/m1/s1
• InChIKey: DMBYYIJBPDWQFF-SCFUHWHPSA-N
• SMILES:
  OpenEye OEToolkits 2.0.7: c1ccc(cc1)CNc2c3c(ncn2)n(cn3)[C@H]4[C@@H]([C@@H]([C@H](O4)COP(=O)(CP(=O)(O)O)O)O)O
  CACTVS 3.385: O[C@H]1[C@@H](O)[C@@H](O[C@@H]1CO[P](O)(=O)C[P](O)(O)=O)n2cnc3c(NCc4ccccc4)ncnc23
  OpenEye OEToolkits 2.0.7: c1ccc(cc1)CNc2c3c(ncn2)n(cn3)C4C(C(C(O4)COP(=O)(CP(=O)(O)O)O)O)O
  CACTVS 3.385: O[CH]1[CH](O)[CH](O[CH]1CO[P](O)(=O)C[P](O)(O)=O)n2cnc3c(NCc4ccccc4)ncnc23
• Formula: C18 H23 N5 O9 P2
• Name: N6-benzyl-(alpha,beta)-methylene-ADP
• ChEMBL: CHEMBL4755577
• PDB chain: 6s7f Chain A Residue 604

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6s7f X-Ray Co-Crystal Structure Guides the Way to Subnanomolar Competitive Ecto-5'-Nucleotidase (CD73) Inhibitors for Cancer Immunotherapy
• Resolution: 2.05 Å
• Binding residue (original residue number in PDB): H38 D85 N117 H118 D121 L184 S185 H243 R354 N390 G392 R395 F417 G447 F500 D506
• Binding residue (residue number reindexed from 1): H13 D60 N92 H93 D96 L159 S160 H218 R329 N358 G360 R363 F385 G415 F468 D474
• Annotation score: 1

Enzymatic activity

• 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:6s7f, PDBe:6s7f, PDBj:6s7f
• PDBsum: 6s7f
• UniProt: P21589|5NTD_HUMAN 5'-nucleotidase (Gene Name=NT5E)