Structure of PDB 8eaq Chain D Binding Site BS10

Receptor Information

>8eaq Chain D (length=2374) Species: 10116 (Rattus norvegicus)

MSSFLHIGDICSLYAEGSTNGFISTLGLVDDRCVVQPEAGDLNNPPKKFR
DCLFKLCPMNRYSAQKQFWKAAKPGANSTTDAVLLNKLHHAADLEKKQNE
TENRKLLGTVIQYGNVIQLLHLKSNKYLTVNKRLPALLEKNAMRVTLDEA
GNEGSWFYIQPFYKLRSIGDSVVIGDKVVLNPVNAGQPLHASSHQLVDNP
GCNEVNSVNCNTSWKIVLFMKWSDNKDDILKGGDVVRLFHAEQEKFLTCD
EHRKKQHVFLRTTGRQSATSATSSKALWEVEVVQHDPCRGGAGYWNSLFR
FKHLATGHYLAAEVDPDFEEECLEKMVYSLVSVPEGNDISSIFELDPTTL
RGGDSLVPRNSYVRLRHLCTNTWVHSTNIPIDKEEEKPVMLKIGTSPLKE
DKEAFAIVPVSPAEVRDLDFANDASKVLGSIAGKLEKGTITQNERRSVTK
LLEDLVYFVTGGTNSGQDVLEVVFSKPNRERQKLMREQNILKQIFKLLQA
PFTDCGDGPMLRLEELGDQRHAPFRHICRLCYRVLRHSQQDYRKNQEYIA
KQFGFMQKQIGYDVLAEDTITALLHNNRKLLEKHITAAEIDTFVSLVRKN
REPRFLDYLSDLCVSMNKSIPVTQELICKAVLNPTNADILIETKLVLSRE
EEVWLFWRDSNKEIRSKSVRELAQDAKEGQKEDRDVLSYYRYQLNLFARM
CLDRQYLAINEISGQLDVDLILRCMSDENLPYDLRASFCRLMLHMHVDRD
PQEQVTPVKYARLWSEIPSEIAIDDYDSSGASKDEIKERFAQTMEFVEEY
LRDVVCQRFPFSDKEKNKLTFEVVNLARNLIYFGFYNFSDLLRLTKILLA
ILDCVHVTTPEKEDIMVMDTKLKIIEILQFILNVRLDYRISCLLCIFKRE
FDESNSQSPGALDFEHIEEQAEGIFGGSEENTPLDLDDHGGRTFLRVLLH
LTMHDYPPLVSGALQLLFRHFSQRQEVLQAFKQVQLLVTSQDVDNYKQIK
QDLDQLRSIVEKSELWVYKSTSSYNYRVVKEILIRLSKLCVQESASVRKS
RKQQQRLLRNMGAHAVVLELLQIPYEKAEDTKMQEIMRLAHEFLQNFCAG
NQQNQALLHKHINLFLNPGILEAVTMQHIFMNNFQLCSEINERVVQHFVH
CIETHGRNVQYIKFLQTIVKAEGKFIKKCQDMVMAELVNSGEDVLVFYND
RASFQTLIQMMRSERDRMDENSPLFMYHIHLVELLAVCTEGKNVYTEIKC
NSLLPLDDIVRVVTHEDCIPEVKIAYINFLNHCYVDTEVEMKEIYTSNHM
WKLFENFLVDICRACNNTSDRKHADSVLEKYVTEIVMSIVTTFFSSPFSD
QSTTLQTRQPVFVQLLQGVFRVYHCNWLMPSQKASVESCIRVLSDVAKSR
AIAIPVDLDSQVNNLFLRDSVLAASRDYRNIIERLQDIVSALEDRLRPLV
QAELSVLVDVLHRPELLFPENTDARRKCESGGFICKLIKHTKQLLEENEE
KLCIKVLQTLREMMTKDRSPPLRQLEDHKRGEALRQILVNRYYGNIRSTS
RGEMSLAEVQCHLDKEGASNLVIDLIMNASSDRVFHESILLAIALLEGGN
TTIQHSFFCRLTEDKKSEKFFKVFYDRMKVAQQEIKATVTVNTSDLGNKK
KDDLEMSAVITIMQPILRFLQLLCENHNRDLQNFLRCQNNKTNYNLVCET
LQFLDCICGSTTGGLGLLGLYINEKNVALINQTLESLTEYCQGPCHENQN
CIATHESNGIDIITALILNDINPLGKKRMDLVLELKNNASKLLLAIMESR
HDSENAERILYNMRPKELVEVIKKAYMQGEVEFEDGENGEDGAASPRNVG
HNIYILAHQLARHNKELQTMLKPGGQVDGDEALEFYAKHTAQIEIVRLDR
TMEQIVFPVPSICEFLTKESKLRIYYTTERDEQGSKINDFFLRSEDLFNE
MNWQKKLRAQPVLYWCARNMSFWSSISFNLAVLMNLLVAFFYPFKGVRGG
TLEPHWLPKPHGIRALIASTILRLIFSVGLQPTLFLLGAFNVCNKIIFLM
SFVGNCGTFTRGYRAMVLDVEFLYHLLYLLICAMGLFVHEFFYSLLLFDL
VYREETLLNVIKSVTRNGRPIILTAALALILVYLFSIVGYLFFKDDFILE
VDRLPNQDKEHTCETLLMCIVTVLSHGLRSGGGVGDVLRKPSKEEPLFAA
RVIYDLLFFFMVIIIVLNLIFGVIIDTFADLRSEKQKKEEILKTTCFICG
LERDKFDNKTVTFEEHIKEEHNMWHYLCFIVLVKVKDSTEYTGPESYVAE
MIRERNLDWFPRMRAMSLVSSDSEGEQNELRNLQEKLESTMKLVTNLSGQ
LSELKDQMTEQRKQKQRIGLLGHP

Ligand information

• Ligand ID: PLX
• InChI: InChI=1S/C42H88NO8P/c1-6-8-10-12-14-16-18-20-21-23-25-27-29-31-33-35-42(45)51-40(39-50-52(46,47)49-37-36-43(3,4)5)38-48-41(44)34-32-30-28-26-24-22-19-17-15-13-11-9-7-2/h40-42,44-45H,6-39H2,1-5H3/p+1/t40-,41+,42+/m1/s1
• InChIKey: YVNJQRQLQPWVSQ-IWSHAHEXSA-O
• SMILES:
  CACTVS 3.341: CCCCCCCCCCCCCCCCC[C@@H](O)O[C@H](CO[C@H](O)CCCCCCCCCCCCCCC)CO[P@@](O)(=O)OCC[N+](C)(C)C
  OpenEye OEToolkits 1.5.0: CCCCCCCCCCCCCCCCCC(O)OC(COC(CCCCCCCCCCCCCCC)O)COP(=O)(O)OCC[N+](C)(C)C
  CACTVS 3.341: CCCCCCCCCCCCCCCCC[CH](O)O[CH](CO[CH](O)CCCCCCCCCCCCCCC)CO[P](O)(=O)OCC[N+](C)(C)C
  ACDLabs 10.04: O=P(OCC(OC(O)CCCCCCCCCCCCCCCCC)COC(O)CCCCCCCCCCCCCCC)(OCC[N+](C)(C)C)O
  OpenEye OEToolkits 1.5.0: CCCCCCCCCCCCCCCCC[C@@H](O)O[C@H](CO[C@@H](CCCCCCCCCCCCCCC)O)CO[P@](=O)(O)OCC[N+](C)(C)C
• Formula: C42 H89 N O8 P
• Name: (9R,11S)-9-({[(1S)-1-HYDROXYHEXADECYL]OXY}METHYL)-2,2-DIMETHYL-5,7,10-TRIOXA-2LAMBDA~5~-AZA-6LAMBDA~5~-PHOSPHAOCTACOSANE-6,6,11-TRIOL
• ZINC: ZINC000058638459
• PDB chain: 8eaq Chain D Residue 5112

Receptor-Ligand Complex Structure

Structure summary

• PDB: 8eaq Conformational motions and ligand-binding underlying gating and regulation in IP 3 R channel.
• Resolution: 3.26 Å
• Binding residue (original residue number in PDB): F2462 L2572
• Binding residue (residue number reindexed from 1): F2142 L2207
• Annotation score: 1

Gene Ontology

Molecular Function

• 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:0005524 ATP binding
• GO:0015278 intracellularly gated calcium channel activity
• GO:0019855 calcium channel inhibitor activity
• GO:0019903 protein phosphatase binding
• GO:0019904 protein domain specific binding
• GO:0035091 phosphatidylinositol binding
• GO:0042802 identical protein binding
• GO:0044325 transmembrane transporter binding
• GO:0044877 protein-containing complex binding
• GO:0046872 metal ion binding
• GO:0070679 inositol 1,4,5 trisphosphate binding
• GO:0098695 inositol 1,4,5-trisphosphate receptor activity involved in regulation of postsynaptic cytosolic calcium levels

Biological Process

• GO:0000902 cell morphogenesis
• GO:0001666 response to hypoxia
• GO:0006811 monoatomic ion transport
• GO:0006816 calcium ion transport
• GO:0006915 apoptotic process
• GO:0007200 phospholipase C-activating G protein-coupled receptor signaling pathway
• GO:0007204 positive regulation of cytosolic calcium ion concentration
• GO:0007207 phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway
• GO:0007338 single fertilization
• GO:0009791 post-embryonic development
• GO:0010976 positive regulation of neuron projection development
• GO:0016358 dendrite development
• GO:0019722 calcium-mediated signaling
• GO:0032024 positive regulation of insulin secretion
• GO:0032469 endoplasmic reticulum calcium ion homeostasis
• GO:0036444 calcium import into the mitochondrion
• GO:0042045 epithelial fluid transport
• GO:0043065 positive regulation of apoptotic process
• GO:0043066 negative regulation of apoptotic process
• GO:0050849 negative regulation of calcium-mediated signaling
• GO:0050882 voluntary musculoskeletal movement
• GO:0051209 release of sequestered calcium ion into cytosol
• GO:0051289 protein homotetramerization
• GO:0051480 regulation of cytosolic calcium ion concentration
• GO:0051928 positive regulation of calcium ion transport
• GO:0055085 transmembrane transport
• GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
• GO:0070588 calcium ion transmembrane transport
• GO:0071320 cellular response to cAMP
• GO:0071456 cellular response to hypoxia
• GO:0097421 liver regeneration
• GO:0099105 ion channel modulating, G protein-coupled receptor signaling pathway
• GO:0099566 regulation of postsynaptic cytosolic calcium ion concentration
• GO:1903514 release of sequestered calcium ion into cytosol by endoplasmic reticulum
• GO:1990806 ligand-gated ion channel signaling pathway
• GO:2000347 positive regulation of hepatocyte proliferation

Cellular Component

• GO:0005635 nuclear envelope
• GO:0005637 nuclear inner membrane
• GO:0005730 nucleolus
• GO:0005737 cytoplasm
• GO:0005783 endoplasmic reticulum
• GO:0005789 endoplasmic reticulum membrane
• GO:0005886 plasma membrane
• GO:0005955 calcineurin complex
• GO:0014069 postsynaptic density
• GO:0016020 membrane
• GO:0016529 sarcoplasmic reticulum
• GO:0030425 dendrite
• GO:0030658 transport vesicle membrane
• GO:0030667 secretory granule membrane
• GO:0030868 smooth endoplasmic reticulum membrane
• GO:0031088 platelet dense granule membrane
• GO:0031094 platelet dense tubular network
• GO:0031410 cytoplasmic vesicle
• GO:0032991 protein-containing complex
• GO:0043025 neuronal cell body
• GO:0045202 synapse
• GO:0048471 perinuclear region of cytoplasm
• GO:0097060 synaptic membrane
• GO:0098685 Schaffer collateral - CA1 synapse
• GO:0098793 presynapse
• GO:0098794 postsynapse
• GO:0098982 GABA-ergic synapse

External links

• PDB: RCSB:8eaq, PDBe:8eaq, PDBj:8eaq
• PDBsum: 8eaq
• PubMed: 36376291
• UniProt: P29994|ITPR1_RAT Inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 (Gene Name=Itpr1)