Structure of PDB 8dve Chain D Binding Site BS01

Receptor Information

>8dve Chain D (length=3942) Species: 9986 (Oryctolagus cuniculus)

VQFLRTDDEVVLQCSATVLKEQLKLCLAAEGFGNRLCFLEPTSNAQNVPP
DLAICCFTLEQSLSVRALQEMLANGHRTLLYGHAILLRHAHSRMYLSCLT
TSRKLAFDVGLQEDATGEACWWTMHPASKQRSEGEKVRVGDDLILVSVSS
ERYLHLSTASGELQVDASFMQTLWNMNPICSCCEEGYVTGGHVLRLFHGE
CLTISAADSDDQRRLVYYEGGAVCTHARSLWRLEPLRISWSGSHLRWGQP
LRIRHVTTGRYLALTEDQGLVVVDACKAHTKATSFCFRVSKEEGMGPPEI
KYGESLCFVQHVASGLWLTYAALKKKAILHQEGHMDDALFLTRCQQEESQ
AARMIHSTAGLYNQFIKGLDSFSGKPRPALPIEAVILSLQDLIGYFEPPS
EELQHEEKQSKLRSLRNRQSLFQEEGMLSLVLNCIDRLNVYTTAAHFAEY
AGEEAAESWKEIVNLLYELLASLIRGNRANCALFSTNLDWVVSKLDRLEA
SSGILEVLYCVLIESPEVLNIIQENHIKSIISLLDKHGRNHKVLDVLCSL
CVCNGVAVRSNQDLITENLLPGRELLLQTNLINYVTSIRPNIFVGRAEGS
TQYGKWYFEVMVDEVVPFLTAQATHLRVGWALTEGYSPYPGGGEGWGGNG
VGDDLYSYGFDGLHLWTGHVARPVTSPGQHLLAPEDVVSCCLDLSVPSIS
FRINGCPVQGVFEAFNLDGLFFPVVSFSAGVKVRFLLGGRHGEFKFLPPP
GYAPCHEAVLPRERLRLEPIKEYRREGPRGPHLVGPSRCLSHTDFVPIVL
PPHLERIREKLAENIHELWALTRILPEPERNYNLQMSGETLKTLLALPAQ
TTLVDRLAENGHNVWARDRVAQGWSYSAVQDIPARRNPRLVPYRLLDEAT
KRSNRDSLCQAVRTLLGYGYNIEPDRVRIFRAEKSYTVQSGRWYFEFEAV
TTGEMRVGWARPELRPDVELGADELAYVFNGHRGQRWHLGSEPFGRPWQS
GDVVGCMIDLTENTIIFTLNGEVLMSDSGSETAFREIEIGDGFLPVCSLG
PGQVGHLNLGQDVSSLRFFAICGLQEGFEPFAINMQRPVTTWFSKSLPQF
EPVPPEHPHYEVARMDGTVDTPPCLRLAHRTWGSQNSLVEMLFLRLSLPV
QFHQHFRDDPEIILNTTTYYYSVRVFAGQEPSCVWVGWVTPDYHQHDMNF
DLSKVRAVTVTMGDEQGNVHSSLKCSNCYMVWGGDFVHTDLVIGCLVDLA
TGLMTFTANGKESNTFFQVEPNTKLFPAVFVLPTHQNVIQFELGKQKNIM
PLSAAMFLSERKNPAPQCPPRLEVQMLMPVSWSRMPNHFLQVETRRAGER
LGWAVQCQDPLTMMALHIPEENRCMDILELSERLDLQRFHSHTLRLYRAV
CALGNNRVAHALCSHVDQAQLLHALEDAHLPGPLRAGYYDLLISIHLESA
CRSRRSMLSEYIVPLTPETRAITLFPPRHGLPGVGVTTSLRPPHHFSPPC
FVAALPAPARLSPAIPLEALRDKALRMLGEAVRDGGQHARDPVGGSVEFQ
FVPVLKLVSTLLVMGIFGDEDVKQILKMIEPEVFTEEEGLLQMKLPESVK
LQMCNLLEYFCDQELQHRVESLAAFAERYVDKLQANQRSRYALLMRAFTM
SAAETARRTREFRSPPQEQINMLLHFKDDCPLPEDIRQDLQDFHQDLLAH
CGIQPQSLQELVSHMVVRWAQEDYVQSPELVRAMFSLLHRQYDGLGELLR
ALPRAYTISPSSVEDTMSLLECLGQIRSLLIVQMGPQEENLMIQSIGNIM
NNKVFYQHPNLMRALGMHETVMEVMVNVLGEIRFPKMVTSCCRFLCYFCR
ISRQNQRSMFDHLSYLLENSGIGLGMQGSTPLDVAAASVIDNNELALALQ
EQDLEKVVSYLAGCGLQSCPMLLAKGYPDIGWNPCGGERYLDFLRFAVFV
NGESVEENANVVVRLLIRKPECFGPALRGEGGSGLLAAIEEAIRISEDPA
RDNRVHLGHAIMSFYAALIDLLGRCAPEMHLIQAGKGEALRIRAILRSLV
PLDDLVGIISLPLQIPVQPKMSASFVPDHKASMVLFLDRVYGIENQDFLL
HVLDVGFLPDMRAAASLDTATFSTTEMALALNRYLCLAVLPLITKCAPLF
AGTEHRAIMVDSMLHTVYRLSRGRSLTKAQRDVIEDCLMALCRYIRPSML
QHLLRRLVFDVPILNEFAKMPLKLLTNHYERCWKYYCLPTGWANFGVTSE
EELHLTRKLFWGIFDSLAHKKYDQELYRMAMPCLCAIAPEKLDSFINKFA
EYTHEKWAFDKIQNNWSYGENVDEELKTHPMLRPYKTFSEKDKEIYRWPI
KESLKAMIAWEWTIEKAREGEEERTEKKKTRKISQTAQTYDPREGYNPQP
PDLSGVTLSRELQAMAEQLAENYHNTWGRKKKQELEAKGGGTHPLLVPYD
TLTAKEKARDREKAQELLKFLQMNGYAVTRIEKRFAFGFLQQLLRWMDIS
QEFIAHLEAHEQEIKFFAKILLPLINQYFTNHCLYFLSNKEKEMITSLFC
KLAALVRHVVNCLHILARKAGLRSFFESASEDIEKMVENLRQNLTYTTVA
LLPVLTTLFQHIAQHDVQVSCYRTLCSIYSLRPALGECLARLAARLMADI
GGLAPHVIEITLPMLCSYLPRWSDHLNSLLGNILRIIVNNRLAVFAQPIV
SRARPELLHSHFIPTIGRLRKRAGKVVAEEEQLRDEFSVLCRDLYALYPL
LIRYVDNNRAHWLTEPNANAEELFRMVGEIFIYWSKSHNFKREEQNFVVQ
NEIVATLKKMLPIGLNMCDQDLIMLAKTRYALKDTDEEVREFLQNDPEKI
VRRVQEVSAVLYHLEQTEHSKQRRRAVVACFRMTPLYNLPTHRACNMFLE
SYKAAWILTEDHSFEDRMIDDLSKAGKKPDPLHQLVLHFSRTALTEKSKL
DEDYLYMAYADIMAKSCHLEEVSFEEKEMEKQRLLYQQSRLHTRGAAEMV
LQMISACKGETGAMVSSTLKLGISILNGGNAEVQQKMLDYLKDKKEVGFF
QSIQALMQTCSVLDLNAFERQNKAEGLGMVNEDGTVINRQNGEKVMADDE
FTQDLFRFLQLLCEGHNNDFQNYLRTQTGNTTTINIIICTVDYLLRLQES
ISDFYWYYSGKDVIEEQGKRNFSKAMSVAKQVFNSLTEYIQGPCTGNQQS
LAHSRLWDAVVGFLHVFAHMMMKLAQDSSQIELLKELLDLQKDMVVMLLS
LLEGNVVNGMIARQMVDMLVESSSNVEMILKFFDMFLKLKDIVGSEAFQD
YVTDPRGLISKKDFQKAMDSQKQFTGPEIQFLLSCSEADENEMINFEEFA
NRFQEPARDIGFNVAVLLTNLSEHVPHDPRLRNFLELAESILEYFRPYLG
RIEIMGASRRIERIYFEISETNRAQWEMPQVKESKRQFIFDVVNEGGEAE
KMELFVSFCEDTIFEMQIAAQISETAREAATALAALLWAVVARWGELEVQ
RVKFLNYLSRNFYTLRFLALFLAFAINFILLFYKVSDSPPNMVYYFLEES
TGYMEPALWCLSLLHTLVAFLCIIGYNCLKVPLVIFKREKELARKLEFDG
LYITEQPGDDDVKGQWDRLVLNTPSFPSNYWDKFVKRKVLDKHGDIFGRE
RIAELLGMDLASLEITAHNERTWLMSIDVKYQIWKFGVIFTDNSFLYLGW
YMVMSLLGHYNNFFFAAHLLDIAMGVKTLRTILSSVTHNGKQLVMTVGLL
AVVVYLYTVVAFNFFRKFYNKSEDEDEPDMKCDDMMTCYLFHMYVGVRAG
GGIGDEIEDPAGDEYELYRVVFDITFFFFVIVILLAIIQGLIIDAFGELR
DQQEQVKEDMETKCFICGIGSDYFDTTPHGFETHTLEEHNLANYMFFLMY
LINKDETEHTGQESYVWKMYQERCWDFFPAGDCFRKQYEDQL

Ligand information

• Ligand ID: CFF
• InChI: InChI=1S/C8H10N4O2/c1-10-4-9-6-5(10)7(13)12(3)8(14)11(6)2/h4H,1-3H3
• InChIKey: RYYVLZVUVIJVGH-UHFFFAOYSA-N
• SMILES:
  CACTVS 3.341: Cn1cnc2N(C)C(=O)N(C)C(=O)c12
  ACDLabs 10.04: O=C2N(c1ncn(c1C(=O)N2C)C)C
  OpenEye OEToolkits 1.5.0: Cn1cnc2c1C(=O)N(C(=O)N2C)C
• Formula: C8 H10 N4 O2
• Name: CAFFEINE;
  3,7-DIHYDRO-1,3,7-TRIMETHYL-1H-PURINE-2,6-DIONE
• ChEMBL: CHEMBL113
• DrugBank: DB00201
• ZINC: ZINC000000001084
• PDB chain: 8dve Chain D Residue 5101

Receptor-Ligand Complex Structure

Structure summary

• PDB: 8dve Cryo-EM analysis of scorpion toxin binding to Ryanodine Receptors reveals subconductance that is abolished by PKA phosphorylation.
• Resolution: 3.84 Å
• Binding residue (original residue number in PDB): W4716 I4996
• Binding residue (residue number reindexed from 1): W3631 I3902
• Annotation score: 1

Gene Ontology

Molecular Function

• GO:0005216 monoatomic ion channel activity
• GO:0005219 ryanodine-sensitive calcium-release channel activity
• GO:0005245 voltage-gated calcium channel activity
• GO:0005262 calcium channel activity
• GO:0005509 calcium ion binding
• GO:0005515 protein binding
• GO:0005516 calmodulin binding
• GO:0005524 ATP binding
• GO:0015278 intracellularly gated calcium channel activity
• GO:0015643 toxic substance binding
• GO:0035381 ATP-gated ion channel activity
• GO:0042802 identical protein binding
• GO:0044325 transmembrane transporter binding
• GO:0046872 metal ion binding
• GO:0097718 disordered domain specific binding

Biological Process

• GO:0003151 outflow tract morphogenesis
• GO:0006811 monoatomic ion transport
• GO:0006816 calcium ion transport
• GO:0006874 intracellular calcium ion homeostasis
• GO:0006936 muscle contraction
• GO:0006941 striated muscle contraction
• GO:0014808 release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
• GO:0019722 calcium-mediated signaling
• GO:0043588 skin development
• GO:0043931 ossification involved in bone maturation
• GO:0048741 skeletal muscle fiber development
• GO:0051209 release of sequestered calcium ion into cytosol
• GO:0051289 protein homotetramerization
• GO:0055085 transmembrane transport
• GO:0070588 calcium ion transmembrane transport
• GO:0071277 cellular response to calcium ion
• GO:0071313 cellular response to caffeine

Cellular Component

• GO:0005790 smooth endoplasmic reticulum
• GO:0014802 terminal cisterna
• GO:0016020 membrane
• GO:0016529 sarcoplasmic reticulum
• GO:0030018 Z disc
• GO:0031090 organelle membrane
• GO:0033017 sarcoplasmic reticulum membrane
• GO:0034704 calcium channel complex
• GO:0042383 sarcolemma
• GO:1990425 ryanodine receptor complex

External links

• PDB: RCSB:8dve, PDBe:8dve, PDBj:8dve
• PDBsum: 8dve
• PubMed: 37224245
• UniProt: P11716|RYR1_RABIT Ryanodine receptor 1 (Gene Name=RYR1)