Structure of PDB 4lts Chain A Binding Site BS01

Receptor Information
>4lts Chain A (length=472) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
EFNILLATDSYKVTHYKQYPPNTSKVYSYFECREKKVKYEETVFYGLQYI
LNKYLKGKVVTKEKIQEAKDVYKEHFQDDVFNEKGWNYILEKYDGHLPIE
IKAVPEGFVIPRGNVLFTVENTDPECYWLTNWIETILVQSWYPITVATNS
REQKKILAKYLLETSGNLDGLEYKLHDFGYRGVSSQETAGIGASAHLVNF
KGTDTVAGLALIKKYYGTKDPVPGYSVPAAEHSTITAWGKDHEKDAFEHI
VTQFSSVPVSVVSDSYDIYNACEKIWGEDLRHLIVSRSTQAPLIIRPDSG
NPLDTVLKVLEILGKKFPVTENSKGYKLLPPYLRVIQGDGVDINTLQEIV
EGMKQKMWSIENIAFGSGGGLLQKLTRDLLNCSFKCSYVVTNGLGINVFK
DPVADPNKRSKKGRLSLHRTPAGNFVTLEEGKGDLEEYGQDLLHTVFKNG
KVTKSYSFDEIRKNAQLNIELE
Ligand information
Ligand IDLTS
InChIInChI=1S/C21H16F3N5O3S/c22-21(23,24)32-17-2-1-3-19(12-17)33(30,31)18-6-4-15(5-7-18)13-27-20(28-14-25)29-16-8-10-26-11-9-16/h1-12H,13H2,(H2,26,27,28,29)
InChIKeyOSHZYJJYBZWSLR-UHFFFAOYSA-N
SMILES
SoftwareSMILES
CACTVS 3.385FC(F)(F)Oc1cccc(c1)[S](=O)(=O)c2ccc(CNC(Nc3ccncc3)=NC#N)cc2
OpenEye OEToolkits 1.7.6c1cc(cc(c1)S(=O)(=O)c2ccc(cc2)CN/C(=N\C#N)/Nc3ccncc3)OC(F)(F)F
ACDLabs 12.01FC(F)(F)Oc1cc(ccc1)S(=O)(=O)c2ccc(cc2)CN/C(=N\C#N)Nc3ccncc3
OpenEye OEToolkits 1.7.6c1cc(cc(c1)S(=O)(=O)c2ccc(cc2)CNC(=NC#N)Nc3ccncc3)OC(F)(F)F
FormulaC21 H16 F3 N5 O3 S
Name2-cyano-1-pyridin-4-yl-3-(4-{[3-(trifluoromethoxy)phenyl]sulfonyl}benzyl)guanidine
ChEMBLCHEMBL3098609
DrugBank
ZINCZINC000095920724
PDB chain4lts Chain A Residue 601 [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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PDB4lts Discovery of potent and efficacious cyanoguanidine-containing nicotinamide phosphoribosyltransferase (Nampt) inhibitors.
Resolution1.692 Å
Binding residue
(original residue number in PDB)		Y188 H191 F193 R196 D219 Y240 S241 V242 A244 S275 R311 I351
Binding residue
(residue number reindexed from 1)		Y173 H176 F178 R181 D204 Y225 S226 V227 A229 S260 R296 I336
Annotation score1
Binding affinityMOAD: ic50=4.4nM
PDBbind-CN: -logKd/Ki=8.36,IC50=4.4nM
BindingDB: IC50=6.20nM
Enzymatic activity
Enzyme Commision number 2.4.2.12: nicotinamide phosphoribosyltransferase.
Gene Ontology
Molecular Function
GO:0005125 cytokine activity
GO:0005515 protein binding
GO:0016757 glycosyltransferase activity
GO:0042802 identical protein binding
GO:0047280 nicotinamide phosphoribosyltransferase activity
Biological Process
GO:0007165 signal transduction
GO:0007267 cell-cell signaling
GO:0007623 circadian rhythm
GO:0008284 positive regulation of cell population proliferation
GO:0008286 insulin receptor signaling pathway
GO:0009435 NAD biosynthetic process
GO:0019363 pyridine nucleotide biosynthetic process
GO:0032922 circadian regulation of gene expression
GO:0034356 NAD biosynthesis via nicotinamide riboside salvage pathway
GO:0045944 positive regulation of transcription by RNA polymerase II
GO:0048511 rhythmic process
GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process
GO:0060612 adipose tissue development
Cellular Component
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0016607 nuclear speck
GO:0030054 cell junction
GO:0070062 extracellular exosome

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:4lts, PDBe:4lts, PDBj:4lts
PDBsum4lts
PubMed24279990
UniProtP43490|NAMPT_HUMAN Nicotinamide phosphoribosyltransferase (Gene Name=NAMPT)

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