Structure of PDB 2uxx Chain A Binding Site BS01

Receptor Information

>2uxx Chain A (length=665) Species: 9606 (Homo sapiens)

PSGVEGAAFQSRLPHDRMTSQEAACFPDIISGPQQTQKVFLFIRNRTLQL
WLDNPKIQLTFEATLQQLEAPYNSDTVLVHRVHSYLERHGLINFGIYKRI
KPLPTKKTGKVIIIGSGVSGLAAARQLQSFGMDVTLLEARDRVGGRVATF
RKGNYVADLGAMVVTGLGGNPMAVVSKQVNMELAKIKQKCPLYEANGQAV
PKEKDEMVEQEFNRLLEATSYLSHQLDFNVLNNKPVSLGQALEVVIQLQE
KHVKDEQIEHWKKIVKTQEELKELLNKMVNLKEKIKELHQQYKEASEVKP
PRDITAEFLVKSKHRDLTALCKEYDELAETQGKLEEKLQELEANPPSDVY
LSSRDRQILDWHFANLEFANATPLSTLSLKHWDQDDDFEFTGSHLTVRNG
YSCVPVALAEGLDIKLNTAVRQVRYTASGCEVIAVNTRSTSQTFIYKCDA
VLCTLPLGVLKQQPPAVQFVPPLPEWKTSAVQRMGFGNLNKVVLCFDRVF
WDPSVNLFGHVGSTTASRGELFLFWNLYKAPILLALVAGEAAGIMENISD
DVIVGRCLAILKGIFGSSAVPQPKETVVSRWRADPWARGSYSYVAAGSSG
NDYDLMAQPITPGPSIPGAPQPIPRLFFAGEHTIRNYPATVHGALLSGLR
EAGRIADQFLGAMYT

Ligand information

• Ligand ID: FAJ
• InChI: InChI=1S/C36H43N9O16P2/c1-16-8-20-21(9-17(16)2)45-25(48)10-19(18-6-4-3-5-7-18)36(45)33(41-35(53)42-34(36)52)43(20)11-22(46)27(49)23(47)12-58-62(54,55)61-63(56,57)59-13-24-28(50)29(51)32(60-24)44-15-40-26-30(37)38-14-39-31(26)44/h3-9,14-15,19,22-25,27-29,32,46-51H,10-13H2,1-2H3,(H,54,55)(H,56,57)(H2,37,38,39)(H,42,52,53)/t19-,22+,23-,24-,25-,27+,28-,29-,32-,36+/m1/s1
• InChIKey: ILGFMEOMSHHKRB-LHVNJQMSSA-N
• SMILES:
  CACTVS 3.385: Cc1cc2N(C[C@H](O)[C@H](O)[C@H](O)CO[P](O)(=O)O[P](O)(=O)OC[C@H]3O[C@H]([C@H](O)[C@@H]3O)n4cnc5c(N)ncnc45)C6=NC(=O)NC(=O)[C@]67[C@H](C[C@@H](O)N7c2cc1C)c8ccccc8
  ACDLabs 12.01: O=C4NC(=O)N=C5N(c1cc(c(cc1N3C(O)CC(c2ccccc2)C345)C)C)CC(O)C(O)C(O)COP(=O)(O)OP(=O)(O)OCC8OC(n7cnc6c(ncnc67)N)C(O)C8O
  OpenEye OEToolkits 1.9.2: Cc1cc2c(cc1C)N3C(CC(C34C(=O)NC(=O)N=C4N2CC(C(C(COP(=O)(O)OP(=O)(O)OCC5C(C(C(O5)n6cnc7c6ncnc7N)O)O)O)O)O)c8ccccc8)O
  OpenEye OEToolkits 1.9.2: Cc1cc2c(cc1C)N3[C@@H](C[C@@H]([C@]34C(=O)NC(=O)N=C4N2C[C@@H]([C@@H]([C@@H](COP(=O)(O)OP(=O)(O)OC[C@@H]5[C@H]([C@H]([C@@H](O5)n6cnc7c6ncnc7N)O)O)O)O)O)c8ccccc8)O
  CACTVS 3.385: Cc1cc2N(C[CH](O)[CH](O)[CH](O)CO[P](O)(=O)O[P](O)(=O)OC[CH]3O[CH]([CH](O)[CH]3O)n4cnc5c(N)ncnc45)C6=NC(=O)NC(=O)[C]67[CH](C[CH](O)N7c2cc1C)c8ccccc8
• Formula: C36 H43 N9 O16 P2
• Name: FAD-trans-2-Phenylcyclopropylamine Adduct;
  FAD-PCPA Adduct
• ZINC: ZINC000263620555
• PDB chain: 2uxx Chain A Residue 900

Receptor-Ligand Complex Structure

Structure summary

• PDB: 2uxx Structural Basis for the Inhibition of the Lsd1 Histone Demethylase by the Antidepressant Trans-2-Phenylcyclopropylamine.
• Resolution: 2.74 Å
• Binding residue (original residue number in PDB): G285 G287 S289 E308 A309 R310 G315 R316 G330 A331 M332 V333 T335 V590 L625 P626 W751 W756 S760 Y761 G800 E801 T810 V811
• Binding residue (residue number reindexed from 1): G115 G117 S119 E138 A139 R140 G145 R146 G160 A161 M162 V163 T165 V420 L455 P456 W581 W586 S590 Y591 G630 E631 T640 V641
• Annotation score: 1
• Binding affinity: PDBbind-CN: -logKd/Ki=3.30,Ki=500uM

Enzymatic activity

• Catalytic site (original residue number in PDB): T335 D553 K661
• Catalytic site (residue number reindexed from 1): T165 D383 K491
• 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:0016491 oxidoreductase activity
• GO:0050660 flavin adenine dinucleotide binding

Biological Process

• GO:0006355 regulation of DNA-templated transcription

Cellular Component

• GO:0005634 nucleus

External links

• PDB: RCSB:2uxx, PDBe:2uxx, PDBj:2uxx
• PDBsum: 2uxx
• PubMed: 17569509
• UniProt: O60341|KDM1A_HUMAN Lysine-specific histone demethylase 1A (Gene Name=KDM1A)