Structure of PDB 2ybk Chain B Binding Site BS02

Receptor Information

>2ybk Chain B (length=349) Species: 9606 (Homo sapiens)

TLNPSARIMTFYPTMEEFRNFSRYIAYIESQGAHRAGLAKVVPPKEWKPR
ASYDDIDDLVIPAPIQQLVTGQSGLFTQYNIQKKAMTVREFRKIANSDKY
CTPRYSEFEELERKYWKNLTFNPPIYGADVNGTLYEKHVDEWNIGRLRTI
LDLVEKESGITIEGVNTPYLYFGMWKTSFAWHTEDMDLYSINYLHFGEPK
SWYSVPPEHGKRLERLAKGFFPGSAQSCEAFLRHKMTLISPLMLKKYGIP
FDKVTQEAGEFMITFPYGYHAGFNHGFNCAESTNFATRRWIEYGKQAVLC
SCRKDMVKISMDVFVRKFQPERYKLWKAGKDNTVIDHTLPTPEAAEFLK

Ligand information

• Ligand ID: 2HG
• InChI: InChI=1S/C5H8O5/c6-3(5(9)10)1-2-4(7)8/h3,6H,1-2H2,(H,7,8)(H,9,10)/t3-/m1/s1
• InChIKey: HWXBTNAVRSUOJR-GSVOUGTGSA-N
• SMILES:
  CACTVS 3.370: O[CH](CCC(O)=O)C(O)=O
  ACDLabs 12.01: O=C(O)CCC(O)C(=O)O
  OpenEye OEToolkits 1.7.0: C(CC(=O)O)C(C(=O)O)O
  OpenEye OEToolkits 1.7.0: C(CC(=O)O)[C@H](C(=O)O)O
  CACTVS 3.370: O[C@H](CCC(O)=O)C(O)=O
• Formula: C5 H8 O5
• Name: (2R)-2-hydroxypentanedioic acid
• ChEMBL: CHEMBL1614745
• ZINC: ZINC000000402968
• PDB chain: 2ybk Chain B Residue 601

Receptor-Ligand Complex Structure

Structure summary

• PDB: 2ybk The oncometabolite 2-hydroxyglutarate inhibits histone lysine demethylases.
• Resolution: 2.4 Å
• Binding residue (original residue number in PDB): Y132 Y177 F185 H188 S196 N198 K206 W208 H276
• Binding residue (residue number reindexed from 1): Y126 Y171 F179 H182 S190 N192 K200 W202 H270
• Annotation score: 2
• Binding affinity: MOAD: ic50=24uM
  BindingDB: IC50=24000nM

Enzymatic activity

• Catalytic site (original residue number in PDB): G170 Y177 H188 E190 H276 S288
• Catalytic site (residue number reindexed from 1): G164 Y171 H182 E184 H270 S282
• Enzyme Commision number: 1.14.11.66: [histone H3]-trimethyl-L-lysine(9) demethylase.
  1.14.11.69: [histone H3]-trimethyl-L-lysine(36) demethylase.

External links

• PDB: RCSB:2ybk, PDBe:2ybk, PDBj:2ybk
• PDBsum: 2ybk
• PubMed: 21460794
• UniProt: O75164|KDM4A_HUMAN Lysine-specific demethylase 4A (Gene Name=KDM4A)