Structure of PDB 4l02 Chain A Binding Site BS01

Receptor Information
>4l02 Chain A (length=360) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
AMGSGVLPRPCRVLVLLNPRGGKGKALQLFRSHVQPLLAEAEISFTLMLT
ERRNHARELVRSEELGRWDALVVMSGDGLMHEVVNGLMERPDWETAIQKP
LCSLPAGSGNALAASLNHYAGYEQVTNEDLLTNCTLLLCRRLLSPMNLLS
LHTASGLRLFSVLSLAWGFIADVDLESEKYRRLGEMRFTLGTFLRLAALR
TYRGRLAYLPVGRVGSKTPASPVVVQQGPVDAHLVPLEEPVPSHWTVVPD
EDFVLVLALLHSHLGSEMFAAPMGRCAAGVMHLFYVRAGVSRAMLLRLFL
AMEKGRHMEYECPYLVYVPVVAFRLEPKDGKGVFAVDGELMVSEAVQGQV
HPNYFWMVSG
Ligand information
Ligand ID1V2
InChIInChI=1S/C23H25Cl2N3O2S/c24-20-6-3-16(11-21(20)25)22-14-31-23(27-22)26-17-4-1-15(2-5-17)7-9-28-10-8-19(30)12-18(28)13-29/h1-6,11,14,18-19,29-30H,7-10,12-13H2,(H,26,27)/t18-,19+/m1/s1
InChIKeySQJKFWCRPARYPY-MOPGFXCFSA-N
SMILES
SoftwareSMILES
OpenEye OEToolkits 1.7.6c1cc(ccc1CCN2CC[C@@H](C[C@@H]2CO)O)Nc3nc(cs3)c4ccc(c(c4)Cl)Cl
CACTVS 3.370OC[C@H]1C[C@@H](O)CCN1CCc2ccc(Nc3scc(n3)c4ccc(Cl)c(Cl)c4)cc2
OpenEye OEToolkits 1.7.6c1cc(ccc1CCN2CCC(CC2CO)O)Nc3nc(cs3)c4ccc(c(c4)Cl)Cl
CACTVS 3.370OC[CH]1C[CH](O)CCN1CCc2ccc(Nc3scc(n3)c4ccc(Cl)c(Cl)c4)cc2
ACDLabs 12.01Clc4ccc(c1nc(sc1)Nc2ccc(cc2)CCN3C(CO)CC(O)CC3)cc4Cl
FormulaC23 H25 Cl2 N3 O2 S
Name(2R,4S)-1-[2-(4-{[4-(3,4-dichlorophenyl)-1,3-thiazol-2-yl]amino}phenyl)ethyl]-2-(hydroxymethyl)piperidin-4-ol
ChEMBLCHEMBL2409865
DrugBank
ZINCZINC000095920759
PDB chain4l02 Chain A Residue 401 [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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PDB4l02 Structure guided design of a series of sphingosine kinase (SphK) inhibitors.
Resolution2.75 Å
Binding residue
(original residue number in PDB)		D81 F173 I174 V177 D178 F192 T196 L268 F288 F303 H311 G342
Binding residue
(residue number reindexed from 1)		D77 F169 I170 V173 D174 F188 T192 L264 F284 F299 H307 G338
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=7.70,IC50=0.02uM
BindingDB: IC50=20nM
Enzymatic activity
Enzyme Commision number 2.3.1.-
2.7.1.91: sphingosine kinase.
Gene Ontology
Molecular Function
GO:0000287 magnesium ion binding
GO:0001727 lipid kinase activity
GO:0003677 DNA binding
GO:0005515 protein binding
GO:0005516 calmodulin binding
GO:0005524 ATP binding
GO:0008289 lipid binding
GO:0008481 sphingosine kinase activity
GO:0016301 kinase activity
GO:0016407 acetyltransferase activity
GO:0017050 D-erythro-sphingosine kinase activity
GO:0038036 sphingosine-1-phosphate receptor activity
GO:0051721 protein phosphatase 2A binding
Biological Process
GO:0001568 blood vessel development
GO:0003376 sphingosine-1-phosphate receptor signaling pathway
GO:0006473 protein acetylation
GO:0006629 lipid metabolic process
GO:0006670 sphingosine metabolic process
GO:0006954 inflammatory response
GO:0007420 brain development
GO:0008283 cell population proliferation
GO:0008284 positive regulation of cell population proliferation
GO:0010800 positive regulation of peptidyl-threonine phosphorylation
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
GO:0016310 phosphorylation
GO:0019722 calcium-mediated signaling
GO:0030100 regulation of endocytosis
GO:0030148 sphingolipid biosynthetic process
GO:0030307 positive regulation of cell growth
GO:0030335 positive regulation of cell migration
GO:0031398 positive regulation of protein ubiquitination
GO:0032651 regulation of interleukin-1 beta production
GO:0032740 positive regulation of interleukin-17 production
GO:0034612 response to tumor necrosis factor
GO:0035556 intracellular signal transduction
GO:0035924 cellular response to vascular endothelial growth factor stimulus
GO:0043066 negative regulation of apoptotic process
GO:0045766 positive regulation of angiogenesis
GO:0045840 positive regulation of mitotic nuclear division
GO:0045931 positive regulation of mitotic cell cycle
GO:0045987 positive regulation of smooth muscle contraction
GO:0046512 sphingosine biosynthetic process
GO:0046521 sphingoid catabolic process
GO:0048146 positive regulation of fibroblast proliferation
GO:0050764 regulation of phagocytosis
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0070301 cellular response to hydrogen peroxide
GO:0071363 cellular response to growth factor stimulus
GO:0071897 DNA biosynthetic process
GO:0090520 sphingolipid mediated signaling pathway
GO:0150077 regulation of neuroinflammatory response
GO:1900060 negative regulation of ceramide biosynthetic process
GO:1900745 positive regulation of p38MAPK cascade
GO:1901224 positive regulation of non-canonical NF-kappaB signal transduction
GO:1903978 regulation of microglial cell activation
GO:1905364 regulation of endosomal vesicle fusion
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005768 endosome
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005905 clathrin-coated pit
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0030139 endocytic vesicle
GO:0031901 early endosome membrane
GO:0043231 intracellular membrane-bounded organelle
GO:0045202 synapse
GO:0098793 presynapse

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4l02, PDBe:4l02, PDBj:4l02
PDBsum4l02
PubMed23845219
UniProtQ9NYA1|SPHK1_HUMAN Sphingosine kinase 1 (Gene Name=SPHK1)

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