Structure of PDB 6m2w Chain A Binding Site BS01

Receptor Information

>6m2w Chain A (length=3949) Species: 9986 (Oryctolagus cuniculus)

QFLRTDDEVVLQCSAEQLKLCLAAEGFGNRLCFLEPTSNAQNVPPDLAIC
CFTLEQSLSVRALQEMLANGHRTLLYGHAILLRHAHSRMYLSCLTTSRSM
TDKLAFDVGLQEDATGEACWWTMHPASKQRSEGEKVRVGDDLILVSVSSE
RYLHLSTASGELQVDASFMQTLWNMNPICSCCEEGYVTGGHVLRLFHECL
TISAQRRLVYYEGGAVCTHARSLWRLEPLRISWSGSHLRWGQPLRIRHVT
TGRYLALVVVDACKAHTKATSFCFRVSKEKLGMGPPEIKYGESLCFVQHV
ASGLWLTYALKKKAILHQEGHMDDALFLTRCQQEESQAARMIHSTAGLYN
QFIKGLDSFSGKPRGPALPIEAVILSLQDLIGYFEPPSEELQHEEKQSKL
RSLRNRQSLFQEEGMLSLVLNCIDRLNVYTTAAHFAEYAGEEAAESWKEI
VNLLYELLASLIRGNRANCALFSTNLDWVVSKLDRLEASSGILEVLYCVL
IESPEVLNIIQENHIKSIISLLDKHGRNHKVLDVLCSLCVCNGVAVRSNQ
DLITENLLPGRELLLQTNLINYVTSIRPNIFVGRAEGSTQYGKWYFEVMV
DEVVPFLTAQATHLRVGWALTEGYSPYPGGGEGWGGNGVGDDLYSYGFDG
LHLWTGHVARPVTSPGQHLLAPEDVVSCCLDLSVPSISFRINGCPVQGVF
EAFNLDGLFFPVVSFSAGVKVRFLLGGRHGEFKFLPPPGYAPCHEAVLPR
ERLRLEPIKEYRREGPRPHLVGPSRCLSHTDFVPCPIVLPPHLERIREKL
AENIHELWALTRIEQGWTYGPVRDDNKRLHPCLVNFHSLPEPERNYNLQM
SGETLKTLLALGCHVGMADEKAEDNLKKTKLPKTYMMSNGYKPAPLDLSH
VRLTPAQTTLVDRLAENGHNVWARDRVAQGWSYSAVQDIPARRNPRLVPY
RLLDEATKRSNRDSLCQAVRTLLGYGYNIEPDRVRIFRAEKSYTVQSGRW
YFEFEAVTTGEMRVGWARPELRPDVELGADELAYVFNGHRGQRWHLGSEP
FGRPWQSGDVVGCMIDLTENTIIFTLNGEVLMSDSGSETAFREIEIGDGF
LPVCSLGPGQVGHLNLGQDVSSLRFFAICGLQEGFEPFAINMQRPVTTWF
SKSLPQFEPVPPEHPHYEVARMDGTVDTPPCLRLAHRTWGSQNSLVEMLF
LRLSLPVQFHQHFRCDDPEIILNTTTYYYSVRVFAGQEPSCVWVGWVTPD
YHQHDMNFDLSKVRAVTVTMGDEQGNVHSSLKCSNCYMVWGGDFVISHTD
LVIGCLVDLATGLMTFTANGKESNTFFQVEPNTKLFPAVFVLPTHQNVIQ
FELGKQKNIMPLSAAMFLSERKNPAPQCPPRLEVQMLMPVSWSRMPNHFL
QVETRRAGERLGWAVQCQDPLTMMALHIPEENRCMDILELSERLDLQRFH
SHTLRLYRAVCALGNNRVAHALCSHVDQAQLLHALEDAHLPGPLRAGYYD
LLISIHLESACRSRRSMLSEYIVPLTPETRAITLFPPGRRHGLPGVGVTT
SLRPPHHFSPPCFVAALPAEAPARLSPAIPLEALRDKALRMLGEAVRDGG
QHARDPVGGSVEFQFVPVLKLVSTLLVMGIFGDEDVKQILKMIEPEVFTE
EEGLLQMKLPESVKLQMCNLLEYFCDQELQHRVESLAAFAERYVDKLQAN
QRSRYALLMRAFTMSAAETARRTREFRSPPQEQINMLLHFKDDCPLPEDI
RQDLQDFHQDLLAHCGIQLEPQSLQELVSHMVVRWAQEDYVQSPELVRAM
FSLLHRQYDGLGELLRALPRAYTISPSSVEDTMSLLECLGQIRSLLIVQM
GPQEENLMIQSIGNIMNNKVFYQHPNLMRALGMHETVMEVMVNVLGEIRF
PKMVTSCCRFLCYFCRISRQNQRSMFDHLSYLLENSGMQGSTPLDVAAAS
VIDNNELALALQEQDLEKVVSYLAGCGLQSCPMLLAKGYPDIGWNPCGGE
RYLDFLRFAVFVNGESVEENANVVVRLLIRKPECFGPALRGSGLLAAIEE
AIRISEDPARDGPNRVHLGHAIMSFYAALIDLLGRCAPEMHLIQAGKGEA
LRIRAILRSLVPLDDLVGIISLPLQIPTLVQPKMSASFVPDHKASMVLFL
DRVYGIENQDFLLHVLDVGFLPDMRAAASLDTEMALALNRYLCLAVLPLI
TKCAPLFAGTEHRAIMVDSMLHTVYRLSRGRSLTKAQRDVIEDCLMALCR
YIRPSMLQHLLRRLVFDVPILNAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAETLNVIIPEKLDSFINKFAEYTHEKWAF
DKIQNNWSYGENVDEELKTHPMLRPYKTFSEKDKEIYRWPIKESLKAMIA
WEWTIEKAREGEYNPQPPDLSGVTLSRELQAMAEQLAENYHNTWGRKKKQ
ELEALVPYDTLTAKEKARDREKAQELLKFLQMNGYAVTRAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAALLSKQRRRAVVACFRMTPLYNLPTHRACNM
FLESYKAAWILTEDHSFEDRMIDDLSKAGEQEKKPDPLHQLVLHFSRTAL
TEKSKLDEDYLYMAYADIMAKSCHLEEEVSFEEKEMEKQRLLYQQSRLHT
RGAAEMVLQMISACKGETGAMVSSTLKLGISILNGGNAEVQQKMLDYLKD
KKEVGFFQSIQALMQTCSVLDLNAFERQNKAEGLGMVNEDGTVINRQNGE
KVMADDEFTQDLFRFLQLLCEGHNNDFQNYLRTQTGNTTTINIIICTVDY
LLRLQESISDFYWYYSGKDVIEEQGKRNFSKAMSVAKQVFNSLTEYIQGP
CTGNQQSLAHSRLWDAVVGFLHVFAHMMMKLAQDSSQIELLKELLDLQKD
MVVMLLSLLEGNVVNGMIARQMVDMLVESSSNVEMILKFFDMFLKLKDIV
GSEAFQDYVTDPRGLISKKDFQKAMDSQKQFTGPEIQFLLSCSEADENEM
INFEEFANRFQEPARDIGFNVAVLLTNLSEHVPHDPRLRNFLELAESILE
YFRPYLGRIEIMGASRRIERIYFEISETNRAQWEMPQVKESKRQFIFDVV
NEGGEAEKMELFVSFCEDTIFEMQIAAQISEAAAAAAAAAAAAAAAAAAA
AAWGELEVQRVKFLNYLSRNFYTLRFLALFLAFAINFILLFYKVSDSPPN
MVYYFLEESTGYMEPALWCLSLLHTLVAFLCIIGYNCLKVPLVIFKREKE
LARKLEFDGLYITEQPDVKGQWDRLVLNTPSFPSNYWDKFVKRKVLDKHG
DIFGRERIAELLGMDLASLEITAHNERTWLMSIDVKYQIWKFGVIFTDNS
FLYLGWYMVMSLLGHYNNFFFAAHLLDIAMGVKTLRTILSSVTHNGKQLV
MTVGLLAVVVYLYTVVAFNFFRKFYNKSEDEDEPDMKCDDMMTCYLFHMY
VGVRAGGGIGDEIEDPAGDEYELYRVVFDITFFFFVIVILLAIIQGLIID
AFGELRDQQEQVKEDMETKCFICGIGSDYFDTTPHGFETHTLEEHNLANY
MFFLMYLINKDETEHTGQESYVWKMYQERCWDFFPAGDCFRKQYEDQLS

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: 6m2w Chain A Residue 5101

Receptor-Ligand Complex Structure

Structure summary

• PDB: 6m2w Structural basis for diamide modulation of ryanodine receptor.
• Resolution: 3.8 Å
• Binding residue (original residue number in PDB): F3753 W4716 I4996 Y5014
• Binding residue (residue number reindexed from 1): F2981 W3637 I3908 Y3926
• 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:6m2w, PDBe:6m2w, PDBj:6m2w
• PDBsum: 6m2w
• PubMed: 32807966
• UniProt: P11716|RYR1_RABIT Ryanodine receptor 1 (Gene Name=RYR1)