Structure of PDB 7u9z Chain C Binding Site BS04

Receptor Information

>7u9z Chain C (length=4226) Species: 9606 (Homo sapiens)

EIQFLRTDDEVVLQCTATIHKEQQKLCLAAEGFGNRLCFLESTSNSKNVP
PDLSICTFVLEQSLSVRALQEMLANHRTLLYGHAILLRHSYSGMYLCCLS
TSRSSTDKLAFDVGLQEDTTGEACWWTIHPASKQRSEGEKVRVGDDLILV
SVSSERYLHLSYGNGSLHVDAAFQQTLWSVAPISSGSEAAQGYLIGGDVL
RLLHGHMDECLTVPSGEHGEEQRRTVHYEGGAVSVHARSLWRLETLRVAW
SGSHIRWGQPFRLRHVTTGKYLSLMEDKNLLLMDKEKADVKSTAFTFRSS
KEKLDVGVRKEVDGMGTSEIKYGDSVCYIQHVDTGLWLTYQSVDSIQRKA
IMHHEGHMDDGISLSRSQHEESRTARVIRSTVFLFNRFIRGLDALSKKAK
ASTVDLPIESVSLSLQDLIGYFHPPDEHLEHEDKQNRLRALKNRQNLFQE
EGMINLVLECIDRLHVYSSAAHFADVAGREAGESWKSILNSLYELLAALI
RGNRKNCAQFSGSLDWLISRLERLEASSGILEVLHCVLVESPEALNIIKE
GHIKSIISLLDKHGRNHKVLDVLCSLCVCHGVAVRSNQHLICDNLLPGRD
LLLQTRLVNHVSSMRPNIFLGVSEGSAQYKKWYYELMVDHTEPFVTAEAT
HLRVGWASTEGYSPYPGGGEEWGGNGVGDDLFSYGFDGLHLWSGCIARTV
SSPNQHLLRTDDVISCCLDLSAPSISFRINGQPVQGMFENFNIDGLFFPV
VSFSAGIKVRFLLGGRHGEFKFLPPPGYAPCYEAVLPKEKLKVEHSREYK
QERTYTRDLLGPTVSLTQAAFTPIPVDTSQIVLPPHLERIREKLAENIHE
LWVMNKIELGWQYGPVRDDNKRQHPCLVEFSKLPEQERNYNLQMSLETLK
TLLALGCHVGISDEHAEDKVKKMKLPKNYQLTSGYKPAPMDLSFIKLTPS
QEAMVDKLAENAHNVWARDRIRQGWTYGIQQDVKNRRNPRLVPYTLLDDR
TKKSNKDSLREAVRTLLGYGYNLEAPDQDHAARAEVCSGTGERFRIFRAE
KTYAVKAGRWYFEFETVTAGDMRVGWSRPGCQPDQELGSDERAFAFDGFK
AQRWHQGNEHYGRSWQAGDVVGCMVDMNEHTMMFTLNGEILLDDSGSELA
FKDFDVGDGFIPVCSLGVAQVGRMNFGKDVSTLKYFTICGLQEGYEPFAV
NTNRDITMWLSKRLPQFLQVPSNHEHIEVTRIDGTIDSSPCLKVTQKSFG
SQNSNTDIMFYRLSMPIECAEVFSKRDDYDFLMQTSTYYYSVRIFPGQEP
ANVWVGWITSDFHQYDTGFDLDRVRTVTVTLGDEKGKVHESIKRSNCYMV
CAGESMSPGQGRNNNGLEIGCVVDAASGLLTFIANGKELSTYYQVEPSTK
LFPAVFAQATSPNVFQFELGRIKNVMPLSAGLFKSEHKNPVPQCPPRLHV
QFLSHVLWSRMPNQFLKVDVSRISERQGWLVQCLDPLQFMSLHIPEENRS
VDILELTEQEELLKFHYHTLRLYSAVCALGNHRVAHALCSHVDEPQLLYA
IENKYMPGLLRAGYYDLLIDIHLSSYATARLMMNNEYIVPMTEETKSITL
FPDENKKHGLPGIGLSTSLRPRMQFSSPSFVSISNECYQYSPEFPLDILK
SKTIQMLTEAVKEGSLHARDPVGGTTEFLFVPLIKLFYTLLIMGIFHNED
LKHILQLIEPSVFKEAPKEGLLQMKLPEPVKLQMCLLLQYLCDCQVRHRI
EAIVAFSDDFVAKLQDNQRFRYNEVMQALNMSAALTARKTKEFRSPPQEQ
INMLLNFKDDKSECPCPEEIRDQLLDFHEDLMTHCGIEKKSSTLQQLISE
TMVRWAQESVIEDPELVRAMFVLLHRQYDGIGGLVRALPKTYTINGVSVE
DTINLLASLGQIRSLLSVRMGKEEEKLMIRGLGDIMNNKVFYQHPNLMRA
LGMHETVMEVMVNVLGGGESKEITFPKMVANCCRFLCYFCRISRQNQKAM
FDHLSYLLENSSVGLASPAMRGSTPLDVAAASVMDNNELALALREPDLEK
VVRYLAGCGLQSCQMLVSKGYPDIGWNPVEGERYLDFLRFAVFCNGESVE
ENANVVVRLLIRRPECFGPALRGEGGNGLLAAMEEAIKIAEDPSRDGPSP
EEDDTIHMGNAIMTFYSALIDLLGRCAPEMHLIHAGKGEAIRIRSILRSL
IPLGDLVGVISIAFQMPTIAKDGNVVEPDMSAGFCPDHKAAMVLFLDSVY
GIEVQDFLLHLLEVGFLPDLRAAASLDTAALSATDMALALNRYLCTAVLP
LLTRCAPLFAGTEHHASLIDSLLHTVYRLSKGCSLTKAQRDSIEVCLLSI
CGQLRPSMMQHLLRRLVFDVPLLNEHAKMPLKLLTNHYERCWKYYCLPGG
WGNFGAASEEELHLSRKLFWGIFDALSQKKYEQELFKLALPCLSAVAGAL
PPDYMESNYVSMMEKQSSMDSEGNFNPQPVDTSNITIPEKLEYFINKYAE
HSHDKWSMDKLANGWIYGEIYSDSSKVQPLMKPYKLLSEKEKEIYRWPIK
ESLKTMLAWGWRIERTREGDSMALYNAAHGYSPRAIDMSNVTLSRDLHAM
AEMMAENYHNIWAKKKKMELESKGGGNHPLLVPYDTLTAKEKAKDREKAQ
DILKFLQINGYAVSRGFKDLELDTPSIEKRFAYSFLQQLIRYVDEAHQYI
LEFDGGSRGKGEHFPYEQEIKFFAKVVLPLIDQYFKNHRLYFLSAASRPL
CSGGHASNKEKEMVTSLFCKLGVLVRHRISLFGNDATSIVNCLHILGQTL
DARTVMKTGLESVKSALRAFLDNAAEDLEKTMENLKQGQFTKGVTQIINY
TTVALLPMLSSLFEHIGQHQFGEDLILEDVQVSCYRILTSLYALGTSKSI
YVERQRSALGECLAAFAGAFPVAFLETHLDKHNIYSIYNTKSSRERAALS
LPTNVEDVCPNIPSLEKLMEEIVELAESGIRYTQMPHVMEVILPMLCSYM
SRWWEHGPENNPERAEMCCTALNSEHMNTLLGNILKIIYNNLGIDEGAWM
KRLAVFSQPIINKVKPQLLKTHFLPLMEKLKKKAATVVSEEVACFRMAPL
YNLPRHRAVNLFLQGYEKSWIETEEHYFEDKLIEDLAKPGAEPPEEDEGT
KRVDPLHQLILLFSRTALTEKCKLEEDFLYMAYADIMAKSCHDEEVKSFE
EKEMEKQKLLYQQARLHDRGAAEMVLQTISASKGETGPMVAATLKLGIAI
LNGGNSTVQQKMLDYLKEKKDVGFFQSLAGLMQSCSVLDLNAFERQNKAE
GLGMVTEEGSGEKVLQDDEFTCDLFRFLQLLCEGHNSDFQNYLRTQTGNN
TTVNIIISTVDYLLRVQESISDFYWYYSGKDVIDEQGQRNFSKAIQVAKQ
VFNTLTEYIQGPCTGNQQSLAHSRLWDAVVGFLHVFAHMQMKLSQDSSQI
ELLKELMDLQKDMVVMLLSMLEGNVVNGTIGKQMVDMLVESSNNVEMILK
FFDMFLKLKDLTSSDTFKEYDPDGKGVISKRDFHKAMESHKHYTQSETEF
LLSCAETDENETLDYEEFVKRFHEPAKDIGFNVAVLLTNLSEHMPNDTRL
QTFLELAESVLNYFQPFLGRIEIMGSAKRIERVYFEISESSRTQWEKPQV
KESKRQFIFDVVNEGGEKEKMELFVNFCEDTIFEMQLAAQISESSILTVR
SALFALRYNILTLMRMLSLKSLKKQMKKVKKMTVKDMVTAFFSSYWSIFM
TLLHFVASVFRGFFRIICFWKKIIAYQQKLLNYFARNFYNMRMLALFVAF
AINFILLFYKVSTIAVHYVLEESSGYMEPTLRILAILHTVISFFCIIGYY
CLKVPLVIFKREKEVARKLEFDGLYITEQPSEDDIKGQWDRLVINTQSFP
NNYWDKFVKRKVMDKYGEFYGRDRISELLGMDKAALDFSDAREKKKPKKD
SSLSAVLNSIDVKYQMWKLGVVFTDNSFLYLAWYMTMSVLGHYNNFFFAA
HLLDIAMGFKTLRTILSSVTHNGKQLVLTVGLLAVVVYLYTVVAFNFFRK
FYNKSEDGDTPDMKCDDMLTCYMFHMYVGVRAGGGIGDEIEDPAGDEYEI
YRIIFDITFFFFVIVILLAIIQGLIIDAFGELRDQQEQVKEDMETKCFIC
GIGNDYFDTVPHGFETHTLQEHNLANYLFFLMYLINKDETEHTGQESYVW
KMYQERCWEFFPAGDCFRKQYEDQLN

Ligand information

• Ligand ID: XAN
• InChI: InChI=1S/C5H4N4O2/c10-4-2-3(7-1-6-2)8-5(11)9-4/h1H,(H3,6,7,8,9,10,11)
• InChIKey: LRFVTYWOQMYALW-UHFFFAOYSA-N
• SMILES:
  CACTVS 3.341: O=C1NC(=O)c2nc[nH]c2N1
  OpenEye OEToolkits 1.5.0: c1[nH]c2c(n1)C(=O)NC(=O)N2
  ACDLabs 10.04: O=C2c1ncnc1NC(=O)N2
• Formula: C5 H4 N4 O2
• Name: XANTHINE
• ChEMBL: CHEMBL1424
• DrugBank: DB02134
• ZINC: ZINC000013517187
• PDB chain: 7u9z Chain C Residue 5004

Receptor-Ligand Complex Structure

Structure summary

• PDB: 7u9z Structural analyses of human ryanodine receptor type 2 channels reveal the mechanisms for sudden cardiac death and treatment.
• Resolution: 3.29 Å
• Binding residue (original residue number in PDB): E4194 W4645 I4926
• Binding residue (residue number reindexed from 1): E3679 W3904 I4185
• Annotation score: 1

Gene Ontology

Molecular Function

• GO:0005216 monoatomic ion channel activity
• GO:0005219 ryanodine-sensitive calcium-release channel activity
• GO:0005262 calcium channel activity
• GO:0005509 calcium ion binding
• GO:0005515 protein binding
• GO:0005516 calmodulin binding
• GO:0015278 intracellularly gated calcium channel activity
• GO:0019899 enzyme binding
• GO:0019901 protein kinase binding
• GO:0034236 protein kinase A catalytic subunit binding
• GO:0034237 protein kinase A regulatory subunit binding
• GO:0042802 identical protein binding
• GO:0043924 suramin binding
• GO:0044325 transmembrane transporter binding
• GO:0048763 calcium-induced calcium release activity
• GO:0097159 organic cyclic compound binding

Biological Process

• GO:0001666 response to hypoxia
• GO:0002027 regulation of heart rate
• GO:0003143 embryonic heart tube morphogenesis
• GO:0003220 left ventricular cardiac muscle tissue morphogenesis
• GO:0003300 cardiac muscle hypertrophy
• GO:0005513 detection of calcium ion
• GO:0006811 monoatomic ion transport
• GO:0006816 calcium ion transport
• GO:0006874 intracellular calcium ion homeostasis
• GO:0006941 striated muscle contraction
• GO:0010460 positive regulation of heart rate
• GO:0010881 regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion
• GO:0010882 regulation of cardiac muscle contraction by calcium ion signaling
• GO:0014808 release of sequestered calcium ion into cytosol by sarcoplasmic reticulum
• GO:0014850 response to muscle activity
• GO:0019722 calcium-mediated signaling
• GO:0031000 response to caffeine
• GO:0035994 response to muscle stretch
• GO:0051209 release of sequestered calcium ion into cytosol
• GO:0051284 positive regulation of sequestering of calcium ion
• GO:0051480 regulation of cytosolic calcium ion concentration
• GO:0051649 establishment of localization in cell
• GO:0051775 response to redox state
• GO:0055085 transmembrane transport
• GO:0055117 regulation of cardiac muscle contraction
• GO:0060048 cardiac muscle contraction
• GO:0060402 calcium ion transport into cytosol
• GO:0070296 sarcoplasmic reticulum calcium ion transport
• GO:0070588 calcium ion transmembrane transport
• GO:0071313 cellular response to caffeine
• GO:0071872 cellular response to epinephrine stimulus
• GO:0072599 establishment of protein localization to endoplasmic reticulum
• GO:0086005 ventricular cardiac muscle cell action potential
• GO:0086029 Purkinje myocyte to ventricular cardiac muscle cell signaling
• GO:0086064 cell communication by electrical coupling involved in cardiac conduction
• GO:0097050 type B pancreatic cell apoptotic process
• GO:0097553 calcium ion transmembrane import into cytosol
• GO:0098735 positive regulation of the force of heart contraction
• GO:0098904 regulation of AV node cell action potential
• GO:0098907 regulation of SA node cell action potential
• GO:0098910 regulation of atrial cardiac muscle cell action potential
• GO:0098911 regulation of ventricular cardiac muscle cell action potential

Cellular Component

• GO:0005790 smooth endoplasmic reticulum
• GO:0005886 plasma membrane
• GO:0014701 junctional sarcoplasmic reticulum membrane
• GO:0016020 membrane
• GO:0016529 sarcoplasmic reticulum
• GO:0030017 sarcomere
• GO:0030018 Z disc
• GO:0032991 protein-containing complex
• GO:0033017 sarcoplasmic reticulum membrane
• GO:0034704 calcium channel complex
• GO:0042383 sarcolemma

External links

• PDB: RCSB:7u9z, PDBe:7u9z, PDBj:7u9z
• PDBsum: 7u9z
• PubMed: 35857850
• UniProt: Q92736|RYR2_HUMAN Ryanodine receptor 2 (Gene Name=RYR2)