Structure of PDB 6ye1 Chain B Binding Site BS03

Receptor Information

>6ye1 Chain B (length=521) Species: 9606 (Homo sapiens)

MWELTILHTNDVHSRLEQTSEDSSKCVDASRCMGGVARLFTKVQQIRRAE
PNVLLLDAGDQYQGTIWFTVYKGAEVAHFMNALRYDAMALGNHEFDNGVE
GLIEPLLKEAKFPILSANIKAKGPLASQISGLYLPYKVLPVGDEVVGIVG
YTSKETPFLSNPGTNLVFEDEITALQPEVDKLKTLNVNKIIALGHSGFEM
DKLIAQKVRGVDVVVGGHSNTFLYTGNPPSKEVPAGKYPFIVTSDDGRKV
PVVQAYAFGKYLGYLKIEFDERGNVISSHGNPILLDSSIPEDPSIKADIN
KWRIKLDDYSTQELGKTIVYLDGSSQSCRFRECNMGNLICDAMINNNLRH
AFWNHVSMCILNGGGIRSPIDERNDGTITWENLAAVLPFGGTFDLVQLKG
STLKKAFEHSVHRYGQSTGEFLQVGGIHVVYDLSRKPGDRVVKLDVLCTK
CRVPSYDPLKMDEVYKVILPNFLANGGDGFQMIKDELLRHDSGDQDINVV
STYISKMKVIYPAVEGRIKFS

Ligand information

• Ligand ID: OO2
• InChI: InChI=1S/C16H23ClN5O7P/c17-16-20-13(19-8-3-1-2-4-8)10-14(21-16)22(6-18-10)15-12(24)11(23)9(29-15)5-28-7-30(25,26)27/h6,8-9,11-12,15,23-24H,1-5,7H2,(H,19,20,21)(H2,25,26,27)/t9-,11-,12-,15-/m1/s1
• InChIKey: ALDWNWOVOJESRL-SDBHATRESA-N
• SMILES:
  OpenEye OEToolkits 2.0.7: c1nc2c(nc(nc2n1[C@H]3[C@@H]([C@@H]([C@H](O3)COCP(=O)(O)O)O)O)Cl)NC4CCCC4
  OpenEye OEToolkits 2.0.7: c1nc2c(nc(nc2n1C3C(C(C(O3)COCP(=O)(O)O)O)O)Cl)NC4CCCC4
  CACTVS 3.385: O[CH]1[CH](O)[CH](O[CH]1COC[P](O)(O)=O)n2cnc3c(NC4CCCC4)nc(Cl)nc23
  CACTVS 3.385: O[C@H]1[C@@H](O)[C@@H](O[C@@H]1COC[P](O)(O)=O)n2cnc3c(NC4CCCC4)nc(Cl)nc23
• Formula: C16 H23 Cl N5 O7 P
• Name: [(2~{R},3~{S},4~{R},5~{R})-5-[2-chloranyl-6-(cyclopentylamino)purin-9-yl]-3,4-bis(oxidanyl)oxolan-2-yl]methoxymethylphosphonic acid
• ChEMBL: CHEMBL4791637
• PDB chain: 6ye1 Chain B Residue 603

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6ye1 Discovery of Potent and Selective Methylenephosphonic Acid CD73 Inhibitors.
• Resolution: 2.66 Å
• Binding residue (original residue number in PDB): H38 D85 N117 H118 L184 S185 H243 R354 N390 G392 R395 F417 G447 F500 D506
• Binding residue (residue number reindexed from 1): H13 D60 N92 H93 L159 S160 H218 R329 N362 G364 R367 F389 G419 F472 D478
• Annotation score: 1

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:6ye1, PDBe:6ye1, PDBj:6ye1
• PDBsum: 6ye1
• PubMed: 33399453
• UniProt: P21589|5NTD_HUMAN 5'-nucleotidase (Gene Name=NT5E)