Structure of PDB 5zya Chain C Binding Site BS01

Receptor Information

>5zya Chain C (length=809) Species: 9606 (Homo sapiens)

EEQKERKIMKLLLKIKNGTPPMRKAALRQITDKAREFGAGPLFNQILPLL
MSPTLEDQERHLLVKVIDRILYKLDDLVRPYVHKILVVIEPLLIDEDYYA
RVEGREIISNLAKAAGLATMISTMRPDIDNMDEYVRNTTARAFAVVASAL
GIPSLLPFLKAVCKSKKSWQARHTGIKIVQQIAILMGCAILPHLRSLVEI
IEHGLVDEQQKVRTISALAIAALAEAATPYGIESFDSVLKPLWKGIRQHR
GKGLAAFLKAIGYLIPLMDAEYANYYTREVMLILIREFQSPDEEMKKIVL
KVVKQCCGTDGVEANYIKTEILPPFFKHFWQHRMALDRRNYRQLVDTTVE
LANKVGAAEIISRIVDDLKDEAEQYRKMVMETIEKIMGNLGAADIDHKLE
EQLIDGILYAFQEQTTEDSVMLNGFGTVVNALGKRVKPYLPQICGTVLWR
LNNKSAKVRQQAADLISRTAVVMKTCQEEKLMGHLGVVLYEYLGEEYPEV
LGSILGALKAIVNVIGMHKMTPPIKDLLPRLTPILKNRHEKVQENCIDLV
GRIADRGAEYVSAREWMRICFELLELLKAHKKAIRRATVNTFGYIAKAIG
PHDVLATLLERQNRVCTTVAIAIVAETCSPFTVLPALMNEYRVPELNVQN
GVLKSLSFLFEYIGEMGKDYIYAVTPLLEDALMDRDLVHRQTASAVVQHM
SLGVYGFGCEDSLNHLLNYVWPNVFETSPHVIQAVMGALEGLRVAIGPCR
MLQYCLQGLFHPARKVRDVYWKIYNSIYIGSQDALIAHYPRIYNDDKNTY
IRYELDYIL

Ligand information

• Ligand ID: 9B0
• InChI: InChI=1S/C40H66N2O9/c1-7-32(44)29(4)37-33(49-37)26-39(5,47)19-12-13-27(2)36-28(3)16-17-34(40(6,48)20-18-31(43)25-35(45)51-36)50-38(46)42-23-21-41(22-24-42)30-14-10-8-9-11-15-30/h12-13,16-17,19,28-34,36-37,43-44,47-48H,7-11,14-15,18,20-26H2,1-6H3/b17-16+,19-12+,27-13+/t28-,29+,31+,32-,33+,34-,36+,37+,39-,40+/m0/s1
• InChIKey: MNOMBFWMICHMKG-MGYWSNOQSA-N
• SMILES:
  OpenEye OEToolkits 2.0.6: CC[C@@H]([C@@H](C)[C@@H]1[C@H](O1)C[C@](C)(/C=C/C=C(\C)/[C@@H]2[C@H](/C=C/[C@@H]([C@](CC[C@H](CC(=O)O2)O)(C)O)OC(=O)N3CCN(CC3)C4CCCCCC4)C)O)O
  OpenEye OEToolkits 2.0.6: CCC(C(C)C1C(O1)CC(C)(C=CC=C(C)C2C(C=CC(C(CCC(CC(=O)O2)O)(C)O)OC(=O)N3CCN(CC3)C4CCCCCC4)C)O)O
  CACTVS 3.385: CC[CH](O)[CH](C)[CH]1O[CH]1C[C](C)(O)C=CC=C(C)[CH]2OC(=O)C[CH](O)CC[C](C)(O)[CH](OC(=O)N3CCN(CC3)C4CCCCCC4)C=C[CH]2C
  CACTVS 3.385: CC[C@H](O)[C@@H](C)[C@H]1O[C@@H]1C[C@@](C)(O)/C=C/C=C(C)/[C@H]2OC(=O)C[C@H](O)CC[C@@](C)(O)[C@@H](OC(=O)N3CCN(CC3)C4CCCCCC4)\C=C\[C@@H]2C
• Formula: C40 H66 N2 O9
• Name: [(2~{S},3~{S},4~{E},6~{S},7~{R},10~{R})-3,7-dimethyl-2-[(2~{E},4~{E},6~{R})-6-methyl-6-oxidanyl-7-[(2~{R},3~{R})-3-[(2~{R},3~{S})-3-oxidanylpentan-2-yl]oxiran-2-yl]hepta-2,4-dien-2-yl]-7,10-bis(oxidanyl)-12-oxidanylidene-1-oxacyclododec-4-en-6-yl] 4-cycloheptylpiperazine-1-carboxylate
• ChEMBL: CHEMBL4297278
• DrugBank: DB12508
• ZINC: ZINC000096179269
• PDB chain: 5zya Chain C Residue 1401

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5zya The cryo-EM structure of the SF3b spliceosome complex bound to a splicing modulator reveals a pre-mRNA substrate competitive mechanism of action
• Resolution: 3.95 Å
• Binding residue (original residue number in PDB): R1075 N1108 V1110 Y1157
• Binding residue (residue number reindexed from 1): R586 N613 V615 Y662
• Annotation score: 1

Gene Ontology

Molecular Function

• GO:0003723 RNA binding
• GO:0003729 mRNA binding
• GO:0005515 protein binding
• GO:1990935 splicing factor binding

Biological Process

• GO:0000245 spliceosomal complex assembly
• GO:0000375 RNA splicing, via transesterification reactions
• GO:0000398 mRNA splicing, via spliceosome
• GO:0006338 chromatin remodeling
• GO:0006397 mRNA processing
• GO:0008380 RNA splicing
• GO:0045943 positive regulation of transcription by RNA polymerase I
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0045945 positive regulation of transcription by RNA polymerase III
• GO:1903241 U2-type prespliceosome assembly

Cellular Component

• GO:0005634 nucleus
• GO:0005654 nucleoplasm
• GO:0005681 spliceosomal complex
• GO:0005684 U2-type spliceosomal complex
• GO:0005686 U2 snRNP
• GO:0005689 U12-type spliceosomal complex
• GO:0005730 nucleolus
• GO:0016607 nuclear speck
• GO:0034693 U11/U12 snRNP
• GO:0071004 U2-type prespliceosome
• GO:0071005 U2-type precatalytic spliceosome
• GO:0071013 catalytic step 2 spliceosome
• GO:0110016 B-WICH complex

External links

• PDB: RCSB:5zya, PDBe:5zya, PDBj:5zya
• PDBsum: 5zya
• PubMed: 29491137
• UniProt: O75533|SF3B1_HUMAN Splicing factor 3B subunit 1 (Gene Name=SF3B1)