Structure of PDB 5lhi Chain A Binding Site BS02

Receptor Information
>5lhi Chain A (length=666) Species: 9606 (Homo sapiens) [Search protein sequence] [Download receptor structure] [Download structure with residue number starting from 1] [View receptor structure]
PSGVEGAAFQSRLPHDRMTSQEAACFPDIISGPQQTQKVFLFIRNRTLQL
WLDNPKIQLTFEATLQQLEAPYNSDTVLVHRVHSYLERHGLINFGIYKRI
KPLPTKKTGKVIIIGSGVSGLAAARQLQSFGMDVTLLEARDRVGGRVATF
RKGNYVADLGAMVVTGLGGNPMAVVSKQVNMELAKIKQKCPLYEANGQAV
PKEKDEMVEQEFNRLLEATSYLSHQLDFNVLNNKPVSLGQALEVVIQLQE
KHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVKP
PRDITAEFLVKSKHRDLTALCKEYDELAETQGKLEEKLQELEANPPSDVY
LSSRDRQILDWHFANLEFANATPLSTLSLKHWDQDDDFEFTGSHLTVRNG
YSCVPVALAEGLDIKLNTAVRQVRYTASGCEVIAVNTRSTSQTFIYKCDA
VLCTLPLGVLKQQPPAVQFVPPLPEWKTSAVQRMGFGNLNKVVLCFDRVF
WDPSVNLFGHVGSTTASRGELFLFWNLYKAPILLALVAGEAAGIMENISD
DVIVGRCLAILKGIFGSSAVPQPKETVVSRWRADPWARGSYSYVAAGSSG
NDYDLMAQPITPGPSIPGAPQPIPRLFFAGEHTIRNYPATVHGALLSGLR
EAGRIADQFLGAMYTL
Ligand information
Ligand ID6X5
InChIInChI=1S/C29H33N3O4S/c1-3-34-18-21-5-4-6-25(31-29(33)27-15-28-26(32(27)2)12-14-37-28)24(21)19-36-23-9-7-22(8-10-23)35-17-20-11-13-30-16-20/h4-10,12,14-15,20,30H,3,11,13,16-19H2,1-2H3,(H,31,33)/t20-/m1/s1
InChIKeySQSNNQXVJVEDMY-HXUWFJFHSA-N
SMILES
SoftwareSMILES
CACTVS 3.385CCOCc1cccc(NC(=O)c2cc3sccc3n2C)c1COc4ccc(OC[C@@H]5CCNC5)cc4
OpenEye OEToolkits 2.0.5CCOCc1cccc(c1COc2ccc(cc2)OC[C@@H]3CCNC3)NC(=O)c4cc5c(n4C)ccs5
CACTVS 3.385CCOCc1cccc(NC(=O)c2cc3sccc3n2C)c1COc4ccc(OC[CH]5CCNC5)cc4
OpenEye OEToolkits 2.0.5CCOCc1cccc(c1COc2ccc(cc2)OCC3CCNC3)NC(=O)c4cc5c(n4C)ccs5
FormulaC29 H33 N3 O4 S
Name~{N}-[3-(ethoxymethyl)-2-[[4-[[(3~{R})-pyrrolidin-3-yl]methoxy]phenoxy]methyl]phenyl]-4-methyl-thieno[3,2-b]pyrrole-5-carboxamide
ChEMBLCHEMBL4090812
DrugBank
ZINCZINC000584905208
PDB chain5lhi Chain A Residue 902 [Download ligand structure] [Download structure with residue number starting from 1] [View ligand structure]
Receptor-Ligand Complex Structure
Global viewLocal viewStructure summary

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PDB5lhi Thieno[3,2-b]pyrrole-5-carboxamides as New Reversible Inhibitors of Histone Lysine Demethylase KDM1A/LSD1. Part 2: Structure-Based Drug Design and Structure-Activity Relationship.
Resolution3.4 Å
Binding residue
(original residue number in PDB)		V333 Q358 F538 A539 D555 H564 W695 Y761 A809
Binding residue
(residue number reindexed from 1)		V163 Q188 F368 A369 D385 H394 W525 Y591 A639
Annotation score1
Binding affinityPDBbind-CN: -logKd/Ki=8.11,IC50=7.8nM
BindingDB: IC50=7.8nM
Enzymatic activity
Catalytic site (original residue number in PDB) T335
Catalytic site (residue number reindexed from 1) T165
Enzyme Commision number 1.14.99.66: [histone-H3]-N(6),N(6)-dimethyl-L-lysine(4) FAD-dependent demethylase.
Gene Ontology
Molecular Function
GO:0002039 p53 binding
GO:0003682 chromatin binding
GO:0003713 transcription coactivator activity
GO:0005515 protein binding
GO:0016491 oxidoreductase activity
GO:0019899 enzyme binding
GO:0030374 nuclear receptor coactivator activity
GO:0032451 demethylase activity
GO:0032452 histone demethylase activity
GO:0032453 histone H3K4 demethylase activity
GO:0032454 histone H3K9 demethylase activity
GO:0042162 telomeric DNA binding
GO:0042802 identical protein binding
GO:0043426 MRF binding
GO:0050660 flavin adenine dinucleotide binding
GO:0050681 nuclear androgen receptor binding
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
GO:0061752 telomeric repeat-containing RNA binding
GO:0140297 DNA-binding transcription factor binding
GO:0140682 FAD-dependent H3K4me/H3K4me3 demethylase activity
GO:1990841 promoter-specific chromatin binding
Biological Process
GO:0000122 negative regulation of transcription by RNA polymerase II
GO:0002052 positive regulation of neuroblast proliferation
GO:0006325 chromatin organization
GO:0006338 chromatin remodeling
GO:0006355 regulation of DNA-templated transcription
GO:0006357 regulation of transcription by RNA polymerase II
GO:0006482 protein demethylation
GO:0010569 regulation of double-strand break repair via homologous recombination
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0010976 positive regulation of neuron projection development
GO:0014070 response to organic cyclic compound
GO:0021987 cerebral cortex development
GO:0031398 positive regulation of protein ubiquitination
GO:0032091 negative regulation of protein binding
GO:0032880 regulation of protein localization
GO:0034644 cellular response to UV
GO:0036211 protein modification process
GO:0042551 neuron maturation
GO:0043392 negative regulation of DNA binding
GO:0043433 negative regulation of DNA-binding transcription factor activity
GO:0043518 negative regulation of DNA damage response, signal transduction by p53 class mediator
GO:0045793 positive regulation of cell size
GO:0045892 negative regulation of DNA-templated transcription
GO:0045944 positive regulation of transcription by RNA polymerase II
GO:0046098 guanine metabolic process
GO:0055001 muscle cell development
GO:0060765 regulation of androgen receptor signaling pathway
GO:0060992 response to fungicide
GO:0071320 cellular response to cAMP
GO:0071480 cellular response to gamma radiation
GO:0090308 regulation of DNA methylation-dependent heterochromatin formation
GO:0120162 positive regulation of cold-induced thermogenesis
GO:0140861 DNA repair-dependent chromatin remodeling
GO:1902166 negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:2000179 positive regulation of neural precursor cell proliferation
GO:2000648 positive regulation of stem cell proliferation
Cellular Component
GO:0000781 chromosome, telomeric region
GO:0000785 chromatin
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005667 transcription regulator complex
GO:0005694 chromosome
GO:0032991 protein-containing complex
GO:1990391 DNA repair complex

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Molecular Function
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Biological Process
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Cellular Component
External links
PDB RCSB:5lhi, PDBe:5lhi, PDBj:5lhi
PDBsum5lhi
PubMed28186757
UniProtO60341|KDM1A_HUMAN Lysine-specific histone demethylase 1A (Gene Name=KDM1A)

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