Structure of PDB 4uxl Chain A Binding Site BS01

Receptor Information
>4uxl Chain A (length=288) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
IENLPAFPREKLTLRLLLGSGAFGEVYEGTAVDILGVGSGEIKVAVKTLK
KGSTDQEKIEFLKEAHLMSKFNHPNILKQLGVCLLNEPQYIILELMEGGD
LLTYLRKARMATFYGPLLTLVDLVDLCVDISKGCVYLERMHFIHRDLAAR
NCLVSVKDYTSPRIVKIGDFGLARDIYKEGLLPVRWMAPESLMDGIFTTQ
SDVWSFGILIWEILTLGHQPYPAHSNLDVLNYVQTGGRLEPPRNCPDDLW
NLMTQCWAQEPDQRPTFHRIQDQLQLFRNFFLNSIYKS
Ligand information
Ligand ID5P8
InChIInChI=1S/C21H19FN6O2/c1-11-15-7-13(22)4-5-14(15)21(29)27(2)10-16-19(17(8-23)28(3)26-16)12-6-18(30-11)20(24)25-9-12/h4-7,9,11H,10H2,1-3H3,(H2,24,25)/t11-/m1/s1
InChIKeyIIXWYSCJSQVBQM-LLVKDONJSA-N
SMILES
SoftwareSMILES
CACTVS 3.385C[CH]1Oc2cc(cnc2N)c3c(CN(C)C(=O)c4ccc(F)cc14)nn(C)c3C#N
ACDLabs 12.01C(#N)c4c3c1cc(c(nc1)N)OC(c2cc(ccc2C(N(Cc3nn4C)C)=O)F)C
CACTVS 3.385C[C@H]1Oc2cc(cnc2N)c3c(CN(C)C(=O)c4ccc(F)cc14)nn(C)c3C#N
OpenEye OEToolkits 1.7.6C[C@@H]1c2cc(ccc2C(=O)N(Cc3c(c(n(n3)C)C#N)-c4cc(c(nc4)N)O1)C)F
OpenEye OEToolkits 1.7.6CC1c2cc(ccc2C(=O)N(Cc3c(c(n(n3)C)C#N)-c4cc(c(nc4)N)O1)C)F
FormulaC21 H19 F N6 O2
Name(10R)-7-amino-12-fluoro-2,10,16-trimethyl-15-oxo-10,15,16,17-tetrahydro-2H-8,4-(metheno)pyrazolo[4,3-h][2,5,11]benzoxadiazacyclotetradecine-3-carbonitrile
ChEMBLCHEMBL3286830
DrugBankDB12130
ZINCZINC000098208524
PDB chain4uxl Chain A Residue 3230 [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]
PDB4uxl Pf-06463922 is a Potent and Selective Next-Generation Ros1/Alk Inhibitor Capable of Blocking Crizotinib-Resistant Ros1 Mutations.
Resolution2.4 Å
Binding residue
(original residue number in PDB)		L1951 A1978 L2026 M2029 G2032 L2086 G2101 K2228 S2229
Binding residue
(residue number reindexed from 1)		L18 A45 L93 M96 G99 L153 G168 K287 S288
Annotation score1
Binding affinityMOAD: Ki<0.025nM
PDBbind-CN: -logKd/Ki=10.60,Ki<0.025nM
Enzymatic activity
Catalytic site (original residue number in PDB) D2079 A2081 R2083 N2084 D2102 E2120
Catalytic site (residue number reindexed from 1) D146 A148 R150 N151 D169 E179
Enzyme Commision number 2.7.10.1: receptor protein-tyrosine kinase.
Gene Ontology
Molecular Function
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005524 ATP binding
Biological Process
GO:0006468 protein phosphorylation
GO:0007169 cell surface receptor protein tyrosine kinase signaling pathway
Cellular Component
GO:0016020 membrane

View graph for
Molecular Function
View graph for
Biological Process
View graph for
Cellular Component
External links
PDB RCSB:4uxl, PDBe:4uxl, PDBj:4uxl
PDBsum4uxl
PubMed25733882
UniProtP08922|ROS1_HUMAN Proto-oncogene tyrosine-protein kinase ROS (Gene Name=ROS1)

[Back to BioLiP]