Structure of PDB 5l01 Chain A Binding Site BS02

Receptor Information
>5l01 Chain A (length=283) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
TVPWFPKKISDLDHCANRVLMYGGFKDNVYRKRRKYFADLAMNYKHGDPI
PKVEFTEEEIKTWGTVFQELNKLYPTHACREYLKNLPLLSKYCGYREDNI
PQLEDVSNFLKERTGFSIRPVAGYLSPRDFLSGLAFRVFHCTQYVRHSSD
PFYTPEPDTCHELLGHVPLLAEPSFAQFSQEIGLASLGASEEAVQKLATC
YFFTVEFGLCKQDGQLRVFGAGLLSSISELKHALSGHAKVKPFDPKITCK
QECLITTFQDVYFVSESFEDAKEKMREFTKTIK
Ligand information
Ligand ID6Z4
InChIInChI=1S/C27H27ClF3N5O3/c28-17-6-7-18(19(12-17)16-4-2-1-3-5-16)23(27(29,30)31)39-22-13-21(34-25(32)35-22)36-10-8-26(9-11-36)14-20(24(37)38)33-15-26/h1-7,12-13,20,23,33H,8-11,14-15H2,(H,37,38)(H2,32,34,35)/t20-,23+/m0/s1
InChIKeyZNSPHKJFQDEABI-NZQKXSOJSA-N
SMILES
SoftwareSMILES
CACTVS 3.385Nc1nc(O[CH](c2ccc(Cl)cc2c3ccccc3)C(F)(F)F)cc(n1)N4CCC5(CC4)CN[CH](C5)C(O)=O
OpenEye OEToolkits 2.0.5c1ccc(cc1)c2cc(ccc2[C@H](C(F)(F)F)Oc3cc(nc(n3)N)N4CCC5(CC4)C[C@H](NC5)C(=O)O)Cl
CACTVS 3.385Nc1nc(O[C@H](c2ccc(Cl)cc2c3ccccc3)C(F)(F)F)cc(n1)N4CCC5(CC4)CN[C@@H](C5)C(O)=O
OpenEye OEToolkits 2.0.5c1ccc(cc1)c2cc(ccc2C(C(F)(F)F)Oc3cc(nc(n3)N)N4CCC5(CC4)CC(NC5)C(=O)O)Cl
FormulaC27 H27 Cl F3 N5 O3
Name(3~{S})-8-[2-azanyl-6-[(1~{R})-1-(4-chloranyl-2-phenyl-phenyl)-2,2,2-tris(fluoranyl)ethoxy]pyrimidin-4-yl]-2,8-diazaspiro[4.5]decane-3-carboxylic acid
ChEMBLCHEMBL4104957
DrugBankDB18478
ZINCZINC000584905275
PDB chain5l01 Chain A Residue 502 [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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PDB5l01 Optimization of spirocyclic proline tryptophan hydroxylase-1 inhibitors.
Resolution1.9 Å
Binding residue
(original residue number in PDB)		Y235 P238 R257 Y264 T265 P266 H272 A309 E317 G333 S336 S337
Binding residue
(residue number reindexed from 1)		Y124 P127 R146 Y153 T154 P155 H161 A198 E206 G222 S225 S226
Annotation score1
Binding affinityMOAD: ic50=33nM
PDBbind-CN: -logKd/Ki=7.48,IC50=33nM
BindingDB: IC50=33nM
Enzymatic activity
Catalytic site (original residue number in PDB) H272 H277 E317 S336
Catalytic site (residue number reindexed from 1) H161 H166 E206 S225
Enzyme Commision number 1.14.16.4: tryptophan 5-monooxygenase.
Gene Ontology
Molecular Function
GO:0004497 monooxygenase activity
GO:0004510 tryptophan 5-monooxygenase activity
GO:0005506 iron ion binding
GO:0005515 protein binding
GO:0016714 oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen
GO:0046872 metal ion binding
Biological Process
GO:0002576 platelet degranulation
GO:0007623 circadian rhythm
GO:0009072 aromatic amino acid metabolic process
GO:0030279 negative regulation of ossification
GO:0035902 response to immobilization stress
GO:0042427 serotonin biosynthetic process
GO:0045600 positive regulation of fat cell differentiation
GO:0046849 bone remodeling
GO:0060749 mammary gland alveolus development
GO:1900046 regulation of hemostasis
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0043005 neuron projection

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:5l01, PDBe:5l01, PDBj:5l01
PDBsum5l01
PubMed28041831
UniProtP17752|TPH1_HUMAN Tryptophan 5-hydroxylase 1 (Gene Name=TPH1)

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