Structure of PDB 5tpg Chain A Binding Site BS02

Receptor Information
>5tpg Chain A (length=271) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
TVPWFPKKISDLDHCNVYRKRRKYFADLAMNYKHGDPIPKVEFTEEEIKT
WGTVFQELNKLYPTHACREYLKNLPLLSKYCGYREDNIPQLEDVSNFLKE
RTGFSIRPVAGYLSPRDFLSGLAFRVFHCTQYVRHSSDPFYTPEPDTCHE
LLGHVPLLAEPSFAQFSQEIGLASLGASEEAVQKLATCYFFTVEFGLCKQ
DGQLRVFGAGLLSSISELKHALSGHAKVKPFDPKITCKQECLITTFQDVY
FVSESFEDAKEKMREFTKTIK
Ligand information
Ligand ID7H5
InChIInChI=1S/C28H29ClF3N5O5S/c1-43(40,41)18-4-2-3-16(11-18)20-12-17(29)5-6-19(20)24(28(30,31)32)42-23-13-22(35-26(33)36-23)37-9-7-27(8-10-37)14-21(25(38)39)34-15-27/h2-6,11-13,21,24,34H,7-10,14-15H2,1H3,(H,38,39)(H2,33,35,36)/t21-,24+/m0/s1
InChIKeyVILFJXJLOMHHDU-XUZZJYLKSA-N
SMILES
SoftwareSMILES
CACTVS 3.385C[S](=O)(=O)c1cccc(c1)c2cc(Cl)ccc2[CH](Oc3cc(nc(N)n3)N4CCC5(CC4)CN[CH](C5)C(O)=O)C(F)(F)F
OpenEye OEToolkits 2.0.6CS(=O)(=O)c1cccc(c1)c2cc(ccc2[C@H](C(F)(F)F)Oc3cc(nc(n3)N)N4CCC5(CC4)C[C@H](NC5)C(=O)O)Cl
CACTVS 3.385C[S](=O)(=O)c1cccc(c1)c2cc(Cl)ccc2[C@@H](Oc3cc(nc(N)n3)N4CCC5(CC4)CN[C@@H](C5)C(O)=O)C(F)(F)F
OpenEye OEToolkits 2.0.6CS(=O)(=O)c1cccc(c1)c2cc(ccc2C(C(F)(F)F)Oc3cc(nc(n3)N)N4CCC5(CC4)CC(NC5)C(=O)O)Cl
ACDLabs 12.01C(C5CC4(CCN(c3cc(OC(c2c(c1cccc(S(=O)(=O)C)c1)cc(cc2)Cl)C(F)(F)F)nc(N)n3)CC4)CN5)(O)=O
FormulaC28 H29 Cl F3 N5 O5 S
Name(3S)-8-(2-amino-6-{(1R)-1-[5-chloro-3'-(methylsulfonyl)[1,1'-biphenyl]-2-yl]-2,2,2-trifluoroethoxy}pyrimidin-4-yl)-2,8-diazaspiro[4.5]decane-3-carboxylic acid
ChEMBLCHEMBL4086156
DrugBank
ZINCZINC000584905458
PDB chain5tpg Chain A Residue 505 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
[Spin on] [Spin off] [Reset]
[High quality] [Low quality]
[White background] [Black background]
PDB5tpg Optimization of spirocyclic proline tryptophan hydroxylase-1 inhibitors.
Resolution1.5 Å
Binding residue
(original residue number in PDB)		Y235 P238 F241 R257 Y264 T265 P266 E267 A309 Y312 E317 S336 S337
Binding residue
(residue number reindexed from 1)		Y112 P115 F118 R134 Y141 T142 P143 E144 A186 Y189 E194 S213 S214
Annotation score1
Binding affinityMOAD: ic50=14nM
PDBbind-CN: -logKd/Ki=7.85,IC50=14nM
BindingDB: IC50=14nM
Enzymatic activity
Catalytic site (original residue number in PDB) H272 H277 E317 S336
Catalytic site (residue number reindexed from 1) H149 H154 E194 S213
Enzyme Commision number 1.14.16.4: tryptophan 5-monooxygenase.
Gene Ontology
Molecular Function
GO:0004497 monooxygenase activity
GO:0005506 iron ion 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
Biological Process
GO:0009072 aromatic amino acid metabolic process

View graph for
Molecular Function
View graph for
Biological Process
External links
PDB RCSB:5tpg, PDBe:5tpg, PDBj:5tpg
PDBsum5tpg
PubMed28041831
UniProtP17752|TPH1_HUMAN Tryptophan 5-hydroxylase 1 (Gene Name=TPH1)

[Back to BioLiP]