Target Information
| Target General Information | Top | |||||
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| Target ID |
T24823
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| Target Name |
Lysine-specific histone demethylase 1B (KDM1B)
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| Synonyms |
Lysine-specific histone demethylase 2; LSD2; Flavin-containing amine oxidase domain-containing protein 1; C6orf193; AOF1
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| Gene Name |
KDM1B
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| Target Type |
Patented-recorded target
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[1] | ||||
| Function |
Required for de novo DNA methylation of a subset of imprinted genes during oogenesis. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Demethylates both mono- and di-methylated 'Lys-4' of histone H3. Has no effect on tri-methylated 'Lys-4', mono-, di- or tri-methylated 'Lys-9', mono-, di- or tri-methylated 'Lys-27', mono-, di- or tri-methylated 'Lys-36' of histone H3, or on mono-, di- or tri-methylated 'Lys-20' of histone H4. Histone demethylase that demethylates 'Lys-4' of histone H3, a specific tag for epigenetic transcriptional activation, thereby acting as a corepressor.
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| BioChemical Class |
CH-NH(2) donor oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.-.-.-
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| Sequence |
MATPRGRTKKKASFDHSPDSLPLRSSGRQAKKKATETTDEDEDGGSEKKYRKCEKAGCTA
TCPVCFASASERCAKNGYTSRWYHLSCGEHFCNECFDHYYRSHKDGYDKYTTWKKIWTSN GKTEPSPKAFMADQQLPYWVQCTKPECRKWRQLTKEIQLTPQIAKTYRCGMKPNTAIKPE TSDHCSLPEDLRVLEVSNHWWYSMLILPPLLKDSVAAPLLSAYYPDCVGMSPSCTSTNRA AATGNASPGKLEHSKAALSVHVPGMNRYFQPFYQPNECGKALCVRPDVMELDELYEFPEY SRDPTMYLALRNLILALWYTNCKEALTPQKCIPHIIVRGLVRIRCVQEVERILYFMTRKG LINTGVLSVGADQYLLPKDYHNKSVIIIGAGPAGLAAARQLHNFGIKVTVLEAKDRIGGR VWDDKSFKGVTVGRGAQIVNGCINNPVALMCEQLGISMHKFGERCDLIQEGGRITDPTID KRMDFHFNALLDVVSEWRKDKTQLQDVPLGEKIEEIYKAFIKESGIQFSELEGQVLQFHL SNLEYACGSNLHQVSARSWDHNEFFAQFAGDHTLLTPGYSVIIEKLAEGLDIQLKSPVQC IDYSGDEVQVTTTDGTGYSAQKVLVTVPLALLQKGAIQFNPPLSEKKMKAINSLGAGIIE KIALQFPYRFWDSKVQGADFFGHVPPSASKRGLFAVFYDMDPQKKHSVLMSVIAGEAVAS VRTLDDKQVLQQCMATLRELFKEQEVPDPTKYFVTRWSTDPWIQMAYSFVKTGGSGEAYD IIAEDIQGTVFFAGEATNRHFPQTVTGAYLSGVREASKIAAF Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Flavin-Adenine Dinucleotide | Ligand Info | |||||
| Structure Description | Crystal structure of LSD2-NPAC with H3(1-26)in space group P21 | PDB:4HSU | ||||
| Method | X-ray diffraction | Resolution | 1.99 Å | Mutation | Yes | [2] |
| PDB Sequence |
GSRKCEKAGC
58 TATCPVCFAS68 ASERCAKNGY78 TSRWYHLSCG88 EHFCNECFDH98 YYRSHKDGYD 108 KYTTWKKIWT118 SNGKTEPSPK128 AFMADQQLPY138 WVQCTKPECR148 KWRQLTKEIQ 158 LTPQIAKTYR168 CGMKSDHCSL187 PEDLRVLEVS197 NHWWYSMLIL207 PPLLKDSVAA 217 PLLSAYYPDC227 VGMSPSCTGM265 NRYFQPFYQP275 NECGKALCVR285 PDVMELDELY 295 EFPEYSRDPT305 MYLALRNLIL315 ALWYTNCKEA325 LTPQKCIPHI335 IVRGLVRIRC 345 VQEVERILYF355 MTRKGLINTG365 VLSVGADQYL375 LPKDYHNKSV385 IIIGAGPAGL 395 AAARQLHNFG405 IKVTVLEAKD415 RIGGRVWDDK425 SFKGVTVGRG435 AQIVNGCINN 445 PVALMCEQLG455 ISMHKFGERC465 DLIQEGGRIT475 DPTIDKRMDF485 HFNALLDVVS 495 EWRKDKTQLQ505 DVPLGEKIEE515 IYKAFIKESG525 IQFSELEGQV535 LQFHLSNLEY 545 ACGSNLHQVS555 ARSWDHNEFF565 AQFAGDHTLL575 TPGYSVIIEK585 LAEGLDIQLK 595 SPVQCIDYSG605 DEVQVTTTDG615 TGYSAQKVLV625 TVPLALLQKG635 AIQFNPPLSE 645 KKMKAINSLG655 AGIIEKIALQ665 FPYRFWDSKV675 QGADFFGHVP685 PSASKRGLFA 695 VFYDMDPQKK705 HSVLMSVIAG715 EAVASVRTLD725 DKQVLQQCMA735 TLRELFKEQE 745 VPDPTKYFVT755 RWSTDPWIQM765 AYSFVKTGGS775 GEAYDIIAED785 IQGTVFFAGE 795 ATNRHFPQTV805 TGAYLSGVRE815 ASKIAAF
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ILE388
3.605
GLY389
3.374
ALA390
3.787
GLY391
3.608
PRO392
3.243
ALA393
2.901
GLY394
4.476
LEU411
3.381
GLU412
2.267
ALA413
3.146
LYS414
3.266
ARG416
4.954
GLY418
3.869
GLY419
3.556
ARG420
2.700
VAL421
4.304
ARG434
3.513
GLY435
3.583
ALA436
3.250
GLN437
3.707
ILE438
3.068
ASN440
4.049
TYR545
4.915
TYR579
3.898
SER596
4.084
PRO597
3.743
VAL598
3.143
THR626
3.815
VAL627
3.399
PRO628
3.550
LEU631
4.294
ILE637
4.204
ILE659
3.864
LYS661
4.088
TRP757
3.532
TRP762
3.228
ILE763
4.289
MET765
4.078
ALA766
3.602
TYR767
3.732
GLY794
3.294
GLU795
3.299
GLN803
2.372
THR804
3.443
VAL805
3.044
THR806
4.726
ALA808
3.232
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 3-(4-Bromophenyl)propanal | Ligand Info | |||||
| Structure Description | Crystal structure of LSD2 in complex with trans-4-Br-PCPA | PDB:7XE2 | ||||
| Method | X-ray diffraction | Resolution | 2.05 Å | Mutation | No | [3] |
| PDB Sequence |
EKKYRKCEKA
56 GCTATCPVCF66 ASASERCAKN76 GYTSRWYHLS86 CGEHFCNECF96 DHYYRSHKDG 106 YDKYTTWKKI116 WTSNGKTEPS126 PKAFMADQQL136 PYWVQCTKPE146 CRKWRQLTKE 156 IQLTPQIAKT166 YRCGMKPNTE180 TSDHCSLPED190 LRVLEVSNHW200 WYSMLILPPL 210 LKDSVAAPLL220 SAYYPDCVGM230 SPSCTSTNRH261 VPGMNRYFQP271 FYQPNECGKA 281 LCVRPDVMEL291 DELYEFPEYS301 RDPTMYLALR311 NLILALWYTN321 CKEALTPQKC 331 IPHIIVRGLV341 RIRCVQEVER351 ILYFMTRKGL361 INTGVLSVGA371 DQYLLPKDYH 381 NKSVIIIGAG391 PAGLAAARQL401 HNFGIKVTVL411 EAKDRIGGRV421 WDDKSFKGVT 431 VGRGAQIVNG441 CINNPVALMC451 EQLGISMHKF461 GERCDLIQEG471 GRITDPTIDK 481 RMDFHFNALL491 DVVSEWRKDK501 TQLQDVPLGE511 KIEEIYKAFI521 KESGIQFSEL 531 EGQVLQFHLS541 NLEYACGSNL551 HQVSARSWDH561 NEFFAQFAGD571 HTLLTPGYSV 581 IIEKLAEGLD591 IQLKSPVQCI601 DYSGDEVQVT611 TTDGTGYSAQ621 KVLVTVPLAL 631 LQKGAIQFNP641 PLSEKKMKAI651 NSLGAGIIEK661 IALQFPYRFW671 DSKVQGADFF 681 GHVPPSASKR691 GLFAVFYDMD701 PQKKHSVLMS711 VIAGEAVASV721 RTLDDKQVLQ 731 QCMATLRELF741 KEQEVPDPTK751 YFVTRWSTDP761 WIQMAYSFVK771 TGGSGEAYDI 781 IAEDIQGTVF791 FAGEATNRHF801 PQTVTGAYLS811 GVREASKIAA821 F |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Similarity Proteins
Human Tissue Distribution
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | LSD1 inhibitors: a patent review (2010-2015).Expert Opin Ther Pat. 2016 May;26(5):565-80. | |||||
| REF 2 | Structural insight into substrate recognition by histone demethylase LSD2/KDM1b. Cell Res. 2013 Feb;23(2):306-9. | |||||
| REF 3 | Structure-Activity Relationship and In Silico Evaluation of cis- and trans-PCPA-Derived Inhibitors of LSD1 and LSD2. doi:10.1021/acsmedchemlett.2c00294. | |||||
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