Structure of PDB 4cxx Chain A Binding Site BS01

Receptor Information
>4cxx Chain A (length=434) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
RGSHMTPKDDEFYQQWQLKYPKLILREASSVSEELHKEVQEAFLTLHKHG
CLFRDLVRIQGKDLLTPVSRILIGNPGCTYKYLNTRLFTVPWPVKGEAEI
AAACETFLKLNDYLQIETIQALEELAAKEKANEDEVDIKSRAAYNVTLLN
FMDPQKMPYLKEEPYFGMGKMAVSWHHDENLVDRSAVAVYSYSCELEGRD
PDIWHVGFKISWDIETPGLAIPLHQGDCYFMLDDLNATHQHCVLAGSQPR
FSSTHRVAECSTGTLDYILQRCQLALQNVCDDVDNDDVSLKSFEPAVLKQ
GEEIHNEVEFEWLRQFWFQRYRKCTDWWCQPMAQLEALWKKMEGVTNAVL
HEVKREGLPVEQRNEILTAILASLTARQNLRREWHARCQSRIARTLPADK
PECRPYWEKDDASMPLPFDLTDIVSELRGQLLEA
Ligand information
Ligand ID640
InChIInChI=1S/C21H23N3O4/c1-21(2,3)16-6-4-14(5-7-16)12-15-10-11-22-13-17(15)20(28)24-23-18(25)8-9-19(26)27/h4-11,13H,12H2,1-3H3,(H,23,25)(H,24,28)(H,26,27)/b9-8+
InChIKeyBNGBOJVHKLUMFE-CMDGGOBGSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6CC(C)(C)c1ccc(cc1)Cc2ccncc2C(=O)NNC(=O)/C=C/C(=O)O
ACDLabs 12.01O=C(c1c(ccnc1)Cc2ccc(cc2)C(C)(C)C)NNC(=O)\C=C\C(=O)O
CACTVS 3.385CC(C)(C)c1ccc(Cc2ccncc2C(=O)NNC(=O)C=CC(O)=O)cc1
CACTVS 3.385CC(C)(C)c1ccc(Cc2ccncc2C(=O)NNC(=O)/C=C/C(O)=O)cc1
OpenEye OEToolkits 1.7.6CC(C)(C)c1ccc(cc1)Cc2ccncc2C(=O)NNC(=O)C=CC(=O)O
FormulaC21 H23 N3 O4
Name(2E)-4-{N'-[4-(4-tert-Butyl-benzyl)-pyridine-3-carbonyl]-hydrazino}-4-oxo-but-2-enoic acid
ChEMBLCHEMBL5289143
DrugBank
ZINCZINC000263620280
PDB chain4cxx Chain A Residue 1505 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB4cxx A strategy based on nucleotide specificity leads to a subfamily-selective and cell-active inhibitor ofN6-methyladenosine demethylase FTO.
Resolution2.76 Å
Binding residue
(original residue number in PDB)		R96 Y106 L109 H231 D233 E234 Y295 H307 V309 R316 S318 R322
Binding residue
(residue number reindexed from 1)		R70 Y80 L83 H176 D178 E179 Y229 H241 V243 R250 S252 R256
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=5.68,IC50=2.11uM
Enzymatic activity
Enzyme Commision number 1.14.11.-
1.14.11.53: mRNA N(6)-methyladenine demethylase.
Gene Ontology
Molecular Function
GO:0008198 ferrous iron binding
GO:0016706 2-oxoglutarate-dependent dioxygenase activity
GO:0016740 transferase activity
GO:0035515 oxidative RNA demethylase activity
GO:0035516 broad specificity oxidative DNA demethylase activity
GO:0046872 metal ion binding
GO:0051213 dioxygenase activity
GO:1990931 mRNA N6-methyladenosine dioxygenase activity
GO:1990984 tRNA demethylase activity
Biological Process
GO:0001659 temperature homeostasis
GO:0006307 DNA alkylation repair
GO:0010883 regulation of lipid storage
GO:0016180 snRNA processing
GO:0040014 regulation of multicellular organism growth
GO:0042245 RNA repair
GO:0044065 regulation of respiratory system process
GO:0060612 adipose tissue development
GO:0061157 mRNA destabilization
GO:0070350 regulation of white fat cell proliferation
GO:0090335 regulation of brown fat cell differentiation
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016607 nuclear speck
GO:0043231 intracellular membrane-bounded organelle

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4cxx, PDBe:4cxx, PDBj:4cxx
PDBsum4cxx
PubMed28553460
UniProtQ9C0B1|FTO_HUMAN Alpha-ketoglutarate-dependent dioxygenase FTO (Gene Name=FTO)

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