Structure of PDB 4h2i Chain A Binding Site BS03

Receptor Information

>4h2i Chain A (length=524) Species: 9606 (Homo sapiens)

MWELTILHTNDVHSRLEQTSEDSSKCVDASRCMGGVARLFTKVQQIRRAE
PNVLLLDAGDQYQGTIWFTVYKGAEVAHFMNALRYDAMALGNHEFDNGVE
GLIEPLLKEAKFPILSANIKAKGPLASQISGLYLPYKVLPVGDEVVGIVG
YTSKETPFLSNPGTNLVFEDEITALQPEVDKLKTLNVNKIIALGHSGFEM
DKLIAQKVRGVDVVVGGHSNTFLYTGNPPSKEVPAGKYPFIVTSDDGRKV
PVVQAYAFGKYLGYLKIEFDERGNVISSHGNPILLDSSIPEDPSIKADIN
KWRIKLDDYSTQELGKTIVYLDGSSQSCRFRECNMGNLICDAMINNNLRH
ADEMFWNHVSMCILNGGGIRSPIDERNDGTITWENLAAVLPFGGTFDLVQ
LKGSTLKKAFEHSVHRYGQSTGEFLQVGGIHVVYDLSRKPGDRVVKLDVL
CTKCRVPSYDPLKMDEVYKVILPNFLANGGDGFQMIKDELLRHDSGDQDI
NVVSTYISKMKVIYPAVEGRIKFS

Ligand information

• Ligand ID: A12
• InChI: InChI=1S/C11H17N5O9P2/c12-9-6-10(14-2-13-9)16(3-15-6)11-8(18)7(17)5(25-11)1-24-27(22,23)4-26(19,20)21/h2-3,5,7-8,11,17-18H,1,4H2,(H,22,23)(H2,12,13,14)(H2,19,20,21)/t5-,7-,8-,11-/m1/s1
• InChIKey: OLCWZBFDIYXLAA-IOSLPCCCSA-N
• SMILES:
  OpenEye OEToolkits 1.5.0: c1nc(c2c(n1)n(cn2)C3C(C(C(O3)COP(=O)(CP(=O)(O)O)O)O)O)N
  CACTVS 3.341: Nc1ncnc2n(cnc12)[CH]3O[CH](CO[P](O)(=O)C[P](O)(O)=O)[CH](O)[CH]3O
  ACDLabs 10.04: O=P(O)(O)CP(=O)(O)OCC3OC(n2cnc1c(ncnc12)N)C(O)C3O
  OpenEye OEToolkits 1.5.0: c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(CP(=O)(O)O)O)O)O)N
  CACTVS 3.341: Nc1ncnc2n(cnc12)[C@@H]3O[C@H](CO[P@](O)(=O)C[P](O)(O)=O)[C@@H](O)[C@H]3O
• Formula: C11 H17 N5 O9 P2
• Name: PHOSPHOMETHYLPHOSPHONIC ACID ADENOSYL ESTER;
  ALPHA,BETA-METHYLENEADENOSINE-5'-DIPHOSPHATE
• ChEMBL: CHEMBL583969
• DrugBank: DB03148
• ZINC: ZINC000013527614
• PDB chain: 4h2i Chain A Residue 603

Receptor-Ligand Complex Structure

Structure summary

• PDB: 4h2i Crystal Structure of the Human Ecto-5'-Nucleotidase (CD73): Insights into the Regulation of Purinergic Signaling.
• Resolution: 2.0 Å
• Binding residue (original residue number in PDB): H38 D85 N117 H118 H243 R354 N390 G392 R395 F417 G447 F500 D506
• Binding residue (residue number reindexed from 1): H13 D60 N92 H93 H218 R329 N365 G367 R370 F392 G422 F475 D481
• 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 R370
• 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:4h2i, PDBe:4h2i, PDBj:4h2i
• PDBsum: 4h2i
• PubMed: 23142347
• UniProt: P21589|5NTD_HUMAN 5'-nucleotidase (Gene Name=NT5E)