Target Binding Site Detail

Target General Information

Target ID

T16739

Target Info

Target Name

Lysine-specific histone demethylase 1 (LSD)

Synonyms

Lysine-specific histone demethylase 1A; LSD1; KIAA0601; KDM1; Flavin-containing amine oxidase domain-containing protein 2; BRAF35-HDAC complex protein BHC110; AOF2

Target Type

Clinical trial Target

Gene Name

KDM1A

Biochemical Class

CH-NH(2) donor oxidoreductase

UniProt ID

KDM1A_HUMAN

Ligand General Information

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Ligand Name

Fad-Trans-2-Phenylcyclopropylamine Adduct

Ligand Info

Canonical SMILES

CC1=CC2=C(C=C1C)N3C(CC(C34C(=O)NC(=O)N=C4N2CC(C(C(COP(=O)(O)OP(=O)(O)OCC5C(C(C(O5)N6C=NC7=C(N=CN=C76)N)O)O)O)O)O)C8=CC=CC=C8)O

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

PubChem Compound ID

16750117

Drug Binding Sites of Target

Top

PDB ID: 2UXX Human LSD1 Histone Demethylase-CoREST in complex with an FAD- tranylcypromine adduct

Method

X-ray diffraction

Resolution

2.74 Å

Mutation

[1]

PDB Sequence

PSGVEGAAFQ

¹⁸⁰

SRLPHDRMTS

¹⁹⁰

QEAACFPDII

²⁰⁰

SGPQQTQKVF

²¹⁰

LFIRNRTLQL

²²⁰

WLDNPKIQLT

²³⁰

FEATLQQLEA

²⁴⁰

PYNSDTVLVH

²⁵⁰

RVHSYLERHG

²⁶⁰

LINFGIYKRI

²⁷⁰

KPLPTKKTGK

²⁸⁰

VIIIGSGVSG

²⁹⁰

LAAARQLQSF

³⁰⁰

GMDVTLLEAR

³¹⁰

DRVGGRVATF

³²⁰

RKGNYVADLG

³³⁰

AMVVTGLGGN

³⁴⁰

PMAVVSKQVN

³⁵⁰

MELAKIKQKC

³⁶⁰

PLYEANGQAV

³⁷⁰

PKEKDEMVEQ

³⁸⁰

EFNRLLEATS

³⁹⁰

YLSHQLDFNV

⁴⁰⁰

LNNKPVSLGQ

⁴¹⁰

ALEVVIQLQE

⁴²⁰

KHVKDEQIEH

⁴³⁰

WKKIVKTQEE

⁴⁴⁰

LKELLNKMVN

⁴⁵⁰

LKEKIKELHQ

⁴⁶⁰

QYKEASEVKP

⁴⁷⁰

PRDITAEFLV

⁴⁸⁰

KSKHRDLTAL

⁴⁹⁰

CKEYDELAET

⁵⁰⁰

QGKLEEKLQE

⁵¹⁰

LEANPPSDVY

⁵²⁰

LSSRDRQILD

⁵³⁰

WHFANLEFAN

⁵⁴⁰

ATPLSTLSLK

⁵⁵⁰

HWDQDDDFEF

⁵⁶⁰

TGSHLTVRNG

⁵⁷⁰

YSCVPVALAE

⁵⁸⁰

GLDIKLNTAV

⁵⁹⁰

RQVRYTASGC

⁶⁰⁰

EVIAVNTRST

⁶¹⁰

SQTFIYKCDA

⁶²⁰

VLCTLPLGVL

⁶³⁰

KQQPPAVQFV

⁶⁴⁰

PPLPEWKTSA

⁶⁵⁰

VQRMGFGNLN

⁶⁶⁰

KVVLCFDRVF

⁶⁷⁰

WDPSVNLFGH

⁶⁸⁰

VGSTTASRGE

⁶⁹⁰

LFLFWNLYKA

⁷⁰⁰

PILLALVAGE

⁷¹⁰

AAGIMENISD

⁷²⁰

DVIVGRCLAI

⁷³⁰

LKGIFGSSAV

⁷⁴⁰

PQPKETVVSR

⁷⁵⁰

WRADPWARGS

⁷⁶⁰

YSYVAAGSSG

⁷⁷⁰

NDYDLMAQPI

⁷⁸⁰

TPGPSIPGAP

⁷⁹⁰

QPIPRLFFAG

⁸⁰⁰

EHTIRNYPAT

⁸¹⁰

VHGALLSGLR

⁸²⁰

EAGRIADQFL

⁸³⁰

GAMYT

Residue

Distance (Å)

ILE284

3.941

GLY285

3.357

SER286

3.924

GLY287

3.575

VAL288

3.495

SER289

2.803

GLY290

4.281

LEU307

3.526

GLU308

2.575

ALA309

3.340

ARG310

3.021

GLY314

3.568

GLY315

3.216

ARG316

2.807

VAL317

3.690

LEU329

3.328

GLY330

3.350

ALA331

3.286

MET332

2.704

VAL333

2.800

THR335

3.342

PHE538

4.137

TYR571

4.914

Residue

Distance (Å)

THR588

3.521

ALA589

3.664

VAL590

2.922

THR624

3.340

LEU625

3.355

PRO626

3.510

VAL629

4.279

VAL637

3.749

LEU659

3.804

LYS661

3.305

TRP751

3.220

PRO755

4.944

TRP756

3.444

GLY759

4.782

SER760

3.648

TYR761

3.348

GLY800

3.317

GLU801

3.003

ALA809

3.322

THR810

2.922

VAL811

3.017

HIS812

4.851

ALA814

3.442

PDB ID: 2Z5U Crystal structure of Lysine-specific histone demethylase 1

Method

X-ray diffraction

Resolution

2.25 Å

Mutation

[2]

PDB Sequence

SGVEGAAFQS

¹⁸¹

RLPHDRMTSQ

¹⁹¹

EAACFPDIIS

²⁰¹

GPQQTQKVFL

²¹¹

FIRNRTLQLW

²²¹

LDNPKIQLTF

²³¹

EATLQQLEAP

²⁴¹

YNSDTVLVHR

²⁵¹

VHSYLERHGL

²⁶¹

INFGIYKRIK

²⁷¹

PLPTKKTGKV

²⁸¹

IIIGSGVSGL

²⁹¹

AAARQLQSFG

³⁰¹

MDVTLLEARD

³¹¹

RVGGRVATFR

³²¹

KGNYVADLGA

³³¹

MVVTGLGGNP

³⁴¹

MAVVSKQVNM

³⁵¹

ELAKIKQKCP

³⁶¹

LYEANGQAVP

³⁷¹

KEKDEMVEQE

³⁸¹

FNRLLEATSY

³⁹¹

LSHQLDFNVL

⁴⁰¹

NNKPVSLGQA

⁴¹¹

LEVVIQLQEK

⁴²¹

HVKDEQIEHW

⁴³¹

KKIVKTQEEL

⁴⁴¹

KELLNKMVNL

⁴⁵¹

KEKIKELHQQ

⁴⁶¹

YKEITAEFLV

⁴⁸⁰

KSKHRDLTAL

⁴⁹⁰

CKEYDELAET

⁵⁰⁰

QGKLEEKLQE

⁵¹⁰

LEANPPSDVY

⁵²⁰

LSSRDRQILD

⁵³⁰

WHFANLEFAN

⁵⁴⁰

ATPLSTLSLK

⁵⁵⁰

HWDQDDDFEF

⁵⁶⁰

TGSHLTVRNG

⁵⁷⁰

YSCVPVALAE

⁵⁸⁰

GLDIKLNTAV

⁵⁹⁰

RQVRYTASGC

⁶⁰⁰

EVIAVNTRST

⁶¹⁰

SQTFIYKCDA

⁶²⁰

VLCTLPLGVL

⁶³⁰

KQQPPAVQFV

⁶⁴⁰

PPLPEWKTSA

⁶⁵⁰

VQRMGFGNLN

⁶⁶⁰

KVVLCFDRVF

⁶⁷⁰

WDPSVNLFGH

⁶⁸⁰

VGSTTASRGE

⁶⁹⁰

LFLFWNLYKA

⁷⁰⁰

PILLALVAGE

⁷¹⁰

AAGIMENISD

⁷²⁰

DVIVGRCLAI

⁷³⁰

LKGIFGSSAV

⁷⁴⁰

PQPKETVVSR

⁷⁵⁰

WRADPWARGS

⁷⁶⁰

YSYVAAGSSG

⁷⁷⁰

NDYDLMAQPI

⁷⁸⁰

TPPIPRLFFA

⁷⁹⁹

GEHTIRNYPA

⁸⁰⁹

TVHGALLSGL

⁸¹⁹

REAGRIADQF

⁸²⁹

Residue

Distance (Å)

ILE284

3.147

GLY285

3.483

SER286

4.192

GLY287

3.613

VAL288

3.405

SER289

2.523

GLY290

4.266

LEU307

2.698

GLU308

2.604

ALA309

3.240

ARG310

3.029

GLY314

3.557

GLY315

3.162

ARG316

2.599

VAL317

3.769

LEU329

3.252

GLY330

3.544

ALA331

3.360

MET332

3.100

VAL333

2.816

THR335

3.334

PHE538

3.726

TYR571

4.747

Residue

Distance (Å)

THR588

3.504

ALA589

4.371

VAL590

3.064

THR624

3.121

LEU625

2.903

PRO626

3.360

VAL629

4.676

VAL637

3.417

LEU659

3.941

LYS661

4.115

TRP751

3.373

TRP756

3.437

GLY759

4.994

SER760

3.741

TYR761

3.501

GLY800

3.248

GLU801

2.910

ALA809

3.002

THR810

3.171

VAL811

2.696

HIS812

4.485

ALA814

3.533

References

Top

REF 1

Structural basis for the inhibition of the LSD1 histone demethylase by the antidepressant trans-2-phenylcyclopropylamine. Biochemistry. 2007 Jul 10;46(27):8058-65.

REF 2

Crystal structure of histone demethylase LSD1 and tranylcypromine at 2.25 A. Biochem Biophys Res Commun. 2008 Feb 1;366(1):15-22.

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