Structure of PDB 8tkd Chain B Binding Site BS02

Receptor Information

>8tkd Chain B (length=2249) Species: 9606 (Homo sapiens)

SSFLHIGDIVSLYAEGSVNGFISTLGLVDDRCVVEPAAGDLDNPPKKFRD
CLFKVCPMNRYSAQKQYWKAKQDVVLLQKLQHAAQMEQKQNDTENKKVHG
DVVKYGSVIQLLHMKSNKYLTVNKRLPALLEKNAMRVTLDATGNEGSWLF
IQPFWKLRSNGDNVVVGDKVILNPVNAGQPLHASNYELSDNAGCKEVNSV
NCNTSWKINLFMQFRDHLEEVLKGGDVVRLFHAEQEKFLTCDEYKGKLQV
FLRTTLRQSATSATSSNALWEVEVVHHDPCRGGAGHWNGLYRFKHLATGN
YLAAEENPSYEKIKYCLVAVPHGNDIASLFELDPTTLQKTDSFVPRNSYV
RLRHLCTNTWIQSTNVPIDIEEERPIRLMLGTCPTKEDKEAFAIVSVPVS
EIRDLDFANDASSMLASAVEKLNEGFISQNDRRFVIQLLEDLVFFVSDVP
NNGQNVLDIMVTKPNRERQKLMREQNILKQVFGILKAPFRPLVRLEELSD
QKNAPYQHMFRLCYRVLRHSQEDYRKNQEHIAKQFGMMQSQIGYDILAED
TITALLHNNRKLLEKHITKTEVETFVSLVRKNREPRFLDYLSDLCVSNHI
AIPVTQELICKCVLDPKNSDILIRTELRPEEVWLTWTDKNNEHHEKSVRQ
LAQEARAGNAHDENVLSYYRYQLKLFARMCLDRQYLAIDEISQQLGVDLI
FLCMADEMLPFDLRASFCHLMLHVHVDRDPQELVTPVKFARLWTEIPTAI
TIKDYDSNLNASRDDKKNKFANTMEFVEDYLNNVVSEAVPFANEEKNKLT
FEVVSLAHNLIYFGFYSFSELLRLTRTLLGIIDDIVVMETKLKILEILQF
ILNVRLDYRISYLLSVFKKEFVEVFPNLDRIGEQAEAMFGSMLEVDDEGG
RMFLRVLIHLTMHDYAPLVSGALQLLFKHFSQRQEAMHTFKQVQLLISAQ
DVENYKVIKSELDRLRTMVEKSELWVDSENYQIVKGILERLNKMCGVGEQ
MRKKQQRLLKNMDAHKVMLDLLQIPYDKGDAKMMEILRYTHQFLQKFCAG
NPGNQALLHKHLHLFLTPGLLEAETMQHIFLNNYQLCSEISEPVLQHFVH
LLATHGRHVQYLDFLHTVIKAEGKYVKKCQDMIMTELTNAGDDVVVFYND
KASLAHLLDMMKAARDGVEDHSPLMYHISLVDLLAACAEGKNVYTEIKCT
SLLPLEDVVSVVTHEDCITEVKMAYVNFVNHCYVDTEVEMKEIYTSNHIW
TLFENFTLDMARVCSKREKRVADPTLEKYVLSVVLDTINAFFSSPFSENS
TSLQTHQTIVVQLLQSTTRLLECPWLQQQHKGSVEACIRTLAMVAKGRAI
LLPMDLDAHISSMLSSGASDYKNIIEKLQDIITALEERLKPLVQAELSVL
VDVLHWPELLFLEGSEAYQRCESGGFLSKLIQHTKDLMESEEKLCIKVLR
TLQQMLLKKTKYGDRGNQLRKMLLQNYLQDWSAIAATQCRLDKEGATKLV
CDLITSTKNEKIFQESIGLAIHLLDGGNTEIQKSFHNLMMSDKKSERFFK
VLHDRMKRAQQETKSTVEMGTSVLIMQPILRFLQLLCENHNRDLQNFLRC
QNNKTNYNLVCETLQFLDIMCGSTTGGLGLLGLYINEDNVGLVIQTLETL
TEYCQGPCHENQTCIVTHESNGIDIITALILNDISPLCKYRMDLVLQLKD
NASKLLLALMESRHDSENAERILISLRPQELVDVIKKAYLQEEERENSEV
SPREVGHNIYILALQLSRHNKQLQHLLKPVEDPLAYYENHTSQIEIVRQD
RSMEQIVFPVPGICQFLTEETKHRLFTTTEQDEQGSKVSDFFDQSSFLHN
EMEWQRKLRSMPLIYWFSRRMTLWGSISFNLAVFINIIIAFFYPYMSIRP
LIVALILRSIYYLGIGPTLNILGALNLTNKIVFVVSFVGNRGTFIRGYKA
MVMDMEFLYHVGYILTSVLGLFAHELFYSILLFDLIYREETLFNVIKSVT
RNGRSILLTALLALILVYLFSIVGFLFLKDDFILEVDRLPDSTERACDTL
LMCIVTVMNHGLRNGGGVGDILRKPSKDESLFPARVVYDLLFFFIVIIIV
LNLIFGVIIDTFADLRSEKQKKEEILKTTCFICGLERDKFDNKTVSFEEH
IKLEHNMWNYLYFIVLVRVKNKTDYTGPESYVAQMIKNKNLDWFPRMRAM
SLVSNEGEGEQNEIRILQDKLNSTMKLVSHLTAQLNELKEQMTEQRKRR

Ligand information

• Ligand ID: I3P
• InChI: InChI=1S/C6H15O15P3/c7-1-2(8)5(20-23(13,14)15)6(21-24(16,17)18)3(9)4(1)19-22(10,11)12/h1-9H,(H2,10,11,12)(H2,13,14,15)(H2,16,17,18)/t1-,2+,3+,4-,5-,6-/m1/s1
• InChIKey: MMWCIQZXVOZEGG-XJTPDSDZSA-N
• SMILES:
  ACDLabs 10.04: O=P(OC1C(O)C(O)C(OP(=O)(O)O)C(O)C1OP(=O)(O)O)(O)O
  OpenEye OEToolkits 1.5.0: C1(C(C(C(C(C1OP(=O)(O)O)O)OP(=O)(O)O)OP(=O)(O)O)O)O
  CACTVS 3.341: O[CH]1[CH](O)[CH](O[P](O)(O)=O)[CH](O[P](O)(O)=O)[CH](O)[CH]1O[P](O)(O)=O
  OpenEye OEToolkits 1.5.0: [C@H]1([C@@H]([C@H]([C@@H]([C@H]([C@@H]1OP(=O)(O)O)O)OP(=O)(O)O)OP(=O)(O)O)O)O
  CACTVS 3.341: O[C@@H]1[C@H](O)[C@@H](O[P](O)(O)=O)[C@H](O[P](O)(O)=O)[C@@H](O)[C@@H]1O[P](O)(O)=O
• Formula: C6 H15 O15 P3
• Name: D-MYO-INOSITOL-1,4,5-TRIPHOSPHATE
• ChEMBL: CHEMBL279107
• DrugBank: DB03401
• ZINC: ZINC000004095598
• PDB chain: 8tkd Chain B Residue 3002

Receptor-Ligand Complex Structure

Structure summary

• PDB: 8tkd Structural titration reveals Ca 2+ -dependent conformational landscape of the IP 3 receptor.
• Resolution: 3.7 Å
• Binding residue (original residue number in PDB): R266 R270 K507 Y567 R568 K569
• Binding residue (residue number reindexed from 1): R253 R257 K470 Y524 R525 K526
• Annotation score: 1

Gene Ontology

Molecular Function

• GO:0000822 inositol hexakisphosphate binding
• GO:0005216 monoatomic ion channel activity
• GO:0005220 inositol 1,4,5-trisphosphate-gated calcium channel activity
• GO:0005262 calcium channel activity
• GO:0005509 calcium ion binding
• GO:0005515 protein binding
• GO:0015278 intracellularly gated calcium channel activity
• GO:0035091 phosphatidylinositol binding
• GO:0043533 inositol 1,3,4,5 tetrakisphosphate binding
• GO:0070679 inositol 1,4,5 trisphosphate binding

Biological Process

• GO:0006811 monoatomic ion transport
• GO:0006816 calcium ion transport
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0007204 positive regulation of cytosolic calcium ion concentration
• GO:0007613 memory
• GO:0019722 calcium-mediated signaling
• GO:0030168 platelet activation
• GO:0050909 sensory perception of taste
• GO:0050913 sensory perception of bitter taste
• GO:0050916 sensory perception of sweet taste
• GO:0050917 sensory perception of umami taste
• GO:0051209 release of sequestered calcium ion into cytosol
• GO:0051289 protein homotetramerization
• GO:0051592 response to calcium ion
• GO:0055074 calcium ion homeostasis
• GO:0055085 transmembrane transport
• GO:0060291 long-term synaptic potentiation
• GO:0070588 calcium ion transmembrane transport

Cellular Component

• GO:0005634 nucleus
• GO:0005640 nuclear outer membrane
• GO:0005654 nucleoplasm
• GO:0005730 nucleolus
• GO:0005737 cytoplasm
• GO:0005783 endoplasmic reticulum
• GO:0005789 endoplasmic reticulum membrane
• GO:0005886 plasma membrane
• GO:0005903 brush border
• GO:0016020 membrane
• GO:0016529 sarcoplasmic reticulum
• GO:0030658 transport vesicle membrane
• GO:0030667 secretory granule membrane
• GO:0031095 platelet dense tubular network membrane
• GO:0031410 cytoplasmic vesicle
• GO:0043025 neuronal cell body
• GO:0043235 receptor complex
• GO:0045177 apical part of cell
• GO:0098554 cytoplasmic side of endoplasmic reticulum membrane

External links

• PDB: RCSB:8tkd, PDBe:8tkd, PDBj:8tkd
• PDBsum: 8tkd
• PubMed: 37898605
• UniProt: Q14573|ITPR3_HUMAN Inositol 1,4,5-trisphosphate-gated calcium channel ITPR3 (Gene Name=ITPR3)