Structure of PDB 8eio Chain A Binding Site BS06

Receptor Information
>8eio Chain A (length=1162) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
MQRSPLEKASVVSKLFFSWTRPILRKGYRQRLELSDIYQIPSVDSADNLS
EKLEREWDRELASKKNPKLINALRRCFFWRFMFYGIFLYLGEVTKAVQPL
LLGRIIASYDPDNKEERSIAIYLGIGLCLLFIVRTLLLHPAIFGLHHIGM
QMRIAMFSLIYKKTLKLSSRVLDKISIGQLVSLLSNNLNKFDEGLALAHF
VWIAPLQVALLMGLIWELLQASAFCGLGFLIVLALFQAGLGRMMMKYRDQ
RAGKISERLVITSEMIENIQSVKAYCWEEAMEKMIENLRQTELKLTRKAA
YVRYFNSSAFFFSGFFVVFLSVLPYALIKGIILRKIFTTISFCIVLRMAV
TRQFPWAVQTWYDSLGAINKIQDFLQKQEYKTLEYNLTTTEVVMENVTAF
WEGTPVLKDINFKIERGQLLAVAGSTGAGKTSLLMVIMGELEPSEGKIKH
SGRISFCSQFSWIMPGTIKENIIGVSYDEYRYRSVIKACQLEEDISKFAE
KDNIVLGEGGITLSGGQRARISLARAVYKDADLYLLDSPFGYLDVLTEKE
IFESCVCKLMANKTRILVTSKMEHLKKADKILILHEGSSYFYGTFSELQN
LWNTYLRYITVHKSLIFVLIWCLVIFLAEVAASLVVLWLLGSYAVIITST
SSYYVFYIYVGVADTLLAMGFFRGLPLVHTLITVSKILHHKMLHSVLQAP
MSTLNTLKAGGILNRFSKDIAILDDLLPLTIFDFIQLLLIVIGAIAVVAV
LQPYIFVATVPVIVAFIMLRAYFLQTSQQLKQLESEGRSPIFTHLVTSLK
GLWTLRAFGRQPYFETLFHKALNLHTANWFLYLSTLRWFQMRIEMIFVIF
FIAVTFISILTTGEGEGRVGIILTLAMNIMSTLQWAVNSSIDVDSLMRSV
SRVFKFIDMPTEGIWPSGGQMTVKDLTAKYTEGGNAILENISFSISPGQR
VGLLGRTGSGKSTLLSAFLRLLNTEGEIQIDGVSWDSITLQQWRKAFGVI
PQKVFIFSGTFRKNLDPYEQWSDQEIWKVADEVGLRSVIEQFPGKLDFVL
VDGGCVLSHGHKQLMCLARSVLSKAKILLLDQPSAHLDPVTYQIIRRTLK
QAFADCTVILCEHRIEAMLECQQFLVIEENKVRQYDSIQKLLNERSLFRQ
AISPSDRVKLFP
Ligand information
Ligand IDVX8
InChIInChI=1S/C24H18F2N2O5/c1-13-5-8-19(27-20(13)14-3-2-4-15(11-14)21(29)30)28-22(31)23(9-10-23)16-6-7-17-18(12-16)33-24(25,26)32-17/h2-8,11-12H,9-10H2,1H3,(H,29,30)(H,27,28,31)
InChIKeyUFSKUSARDNFIRC-UHFFFAOYSA-N
SMILES
SoftwareSMILES
CACTVS 3.385Cc1ccc(NC(=O)C2(CC2)c3ccc4OC(F)(F)Oc4c3)nc1c5cccc(c5)C(O)=O
ACDLabs 12.01O=C(O)c1cccc(c1)c1nc(ccc1C)NC(=O)C1(CC1)c1ccc2OC(F)(F)Oc2c1
OpenEye OEToolkits 2.0.7Cc1ccc(nc1c2cccc(c2)C(=O)O)NC(=O)C3(CC3)c4ccc5c(c4)OC(O5)(F)F
FormulaC24 H18 F2 N2 O5
NameLumacaftor;
3-(6-{[1-(2,2-difluoro-2H-1,3-benzodioxol-5-yl)cyclopropane-1-carbonyl]amino}-3-methylpyridin-2-yl)benzoic acid;
VX-809
ChEMBLCHEMBL2103870
DrugBankDB09280
ZINCZINC000064033452
PDB chain8eio Chain A Residue 1507 [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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PDB8eio Molecular structures reveal synergistic rescue of Delta 508 CFTR by Trikafta modulators.
Resolution2.8 Å
Binding residue
(original residue number in PDB)		K68 I70 R74 F77 F81 A198 W361 S364
Binding residue
(residue number reindexed from 1)		K68 I70 R74 F77 F81 A198 W361 S364
Annotation score1
Enzymatic activity
Enzyme Commision number 5.6.1.6: channel-conductance-controlling ATPase.
Gene Ontology
Molecular Function
GO:0005254 chloride channel activity
GO:0005260 intracellularly ATP-gated chloride channel activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0015106 bicarbonate transmembrane transporter activity
GO:0015108 chloride transmembrane transporter activity
GO:0016853 isomerase activity
GO:0016887 ATP hydrolysis activity
GO:0017081 chloride channel regulator activity
GO:0019869 chloride channel inhibitor activity
GO:0019899 enzyme binding
GO:0030165 PDZ domain binding
GO:0042626 ATPase-coupled transmembrane transporter activity
GO:0043225 ATPase-coupled inorganic anion transmembrane transporter activity
GO:0051087 protein-folding chaperone binding
GO:0071889 14-3-3 protein binding
GO:0106138 Sec61 translocon complex binding
GO:0140359 ABC-type transporter activity
Biological Process
GO:0006695 cholesterol biosynthetic process
GO:0006811 monoatomic ion transport
GO:0006821 chloride transport
GO:0006904 vesicle docking involved in exocytosis
GO:0015701 bicarbonate transport
GO:0030301 cholesterol transport
GO:0034220 monoatomic ion transmembrane transport
GO:0034976 response to endoplasmic reticulum stress
GO:0035377 transepithelial water transport
GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0045921 positive regulation of exocytosis
GO:0048240 sperm capacitation
GO:0050891 multicellular organismal-level water homeostasis
GO:0051454 intracellular pH elevation
GO:0051649 establishment of localization in cell
GO:0055085 transmembrane transport
GO:0060081 membrane hyperpolarization
GO:0070175 positive regulation of enamel mineralization
GO:0071320 cellular response to cAMP
GO:0097186 amelogenesis
GO:1902161 positive regulation of cyclic nucleotide-gated ion channel activity
GO:1902476 chloride transmembrane transport
GO:1902943 positive regulation of voltage-gated chloride channel activity
GO:1904322 cellular response to forskolin
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005765 lysosomal membrane
GO:0005768 endosome
GO:0005769 early endosome
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0009986 cell surface
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016324 apical plasma membrane
GO:0030660 Golgi-associated vesicle membrane
GO:0030669 clathrin-coated endocytic vesicle membrane
GO:0031901 early endosome membrane
GO:0032991 protein-containing complex
GO:0034707 chloride channel complex
GO:0055037 recycling endosome
GO:0055038 recycling endosome membrane

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:8eio, PDBe:8eio, PDBj:8eio
PDBsum8eio
PubMed36264792
UniProtP13569|CFTR_HUMAN Cystic fibrosis transmembrane conductance regulator (Gene Name=CFTR)

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