Structure of PDB 5ek3 Chain A Binding Site BS01

Receptor Information

>5ek3 Chain A (length=374) Species: 9606 (Homo sapiens)

SKEYHIDEEVGFALPNPQENLPDFYNDWMFIAKHLPDLIESGQLRERVEK
LNMLSIDHLTDHKSQRLARLVLGCITMAYVWGKGHGDVRKVLPRNIAVPY
CQLSKKLELPPILVYADCVLANWKKKDPNKPLTYENMDVLFSFRDGDCSK
GFFLVSLLVEIAAASAIKVIPTVFKAMQMQERDTLLKALLEIASCLEKAL
QVFHQIHDHVNPKAFFSVLRIYLSGWKGNPQLSDGLVYEGFWEDPKEFAG
GSAGQSSVFQCFDVLLGIQQTAGGGHAAQFLQDMRRYMPPAHRNFLCSLE
SNPSVREFVLSKGDAGLREAYDACVKALVSLRSYHLQIVTKYILIPASQQ
GGTDLMNFLKTVRSTTEKSLLKEG

Ligand information

• Ligand ID: HEM
• InChI: InChI=1S/C34H34N4O4.Fe/c1-7-21-17(3)25-13-26-19(5)23(9-11-33(39)40)31(37-26)16-32-24(10-12-34(41)42)20(6)28(38-32)15-30-22(8-2)18(4)27(36-30)14-29(21)35-25;/h7-8,13-16H,1-2,9-12H2,3-6H3,(H4,35,36,37,38,39,40,41,42);/q;+2/p-2/b25-13-,26-13-,27-14-,28-15-,29-14-,30-15-,31-16-,32-16-;
• InChIKey: KABFMIBPWCXCRK-RGGAHWMASA-L
• SMILES:
  OpenEye OEToolkits 1.7.6: Cc1c2n3c(c1CCC(=O)O)C=C4C(=C(C5=[N]4[Fe]36[N]7=C(C=C8N6C(=C5)C(=C8C)C=C)C(=C(C7=C2)C)C=C)C)CCC(=O)O
  CACTVS 3.385: CC1=C(CCC(O)=O)C2=Cc3n4[Fe]5|6|N2=C1C=c7n5c(=CC8=N|6C(=Cc4c(C)c3CCC(O)=O)C(=C8C=C)C)c(C)c7C=C
  ACDLabs 12.01: C=1c3c(c(c4C=C5C(=C(C=6C=C7C(=C(C8=CC=2C(=C(C=1N=2[Fe](n34)(N5=6)N78)CCC(=O)O)C)\C=C)C)\C=C)C)C)CCC(=O)O
• Formula: C34 H32 Fe N4 O4
• Name: PROTOPORPHYRIN IX CONTAINING FE;
  HEME
• DrugBank: DB18267
• PDB chain: 5ek3 Chain A Residue 501

Receptor-Ligand Complex Structure

Structure summary

• PDB: 5ek3 Important Hydrogen Bond Networks in Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor Design Revealed by Crystal Structures of Imidazoleisoindole Derivatives with IDO1
• Resolution: 2.209 Å
• Binding residue (original residue number in PDB): F163 S167 V170 F214 I217 F226 S263 A264 F270 F291 R343 H346 I349 V350 Y353 I354 L388 V391
• Binding residue (residue number reindexed from 1): F152 S156 V159 F203 I206 F215 S252 A253 F259 F280 R332 H335 I338 V339 Y342 I343 L359 V362
• Annotation score: 1

Enzymatic activity

• Enzyme Commision number: 1.13.11.52: indoleamine 2,3-dioxygenase.

Gene Ontology

Molecular Function

• GO:0004833 tryptophan 2,3-dioxygenase activity
• GO:0009055 electron transfer activity
• GO:0016702 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen
• GO:0020037 heme binding
• GO:0033754 indoleamine 2,3-dioxygenase activity
• GO:0046872 metal ion binding
• GO:0051213 dioxygenase activity

Biological Process

• GO:0002376 immune system process
• GO:0002666 positive regulation of T cell tolerance induction
• GO:0002678 positive regulation of chronic inflammatory response
• GO:0002830 positive regulation of type 2 immune response
• GO:0006569 tryptophan catabolic process
• GO:0006954 inflammatory response
• GO:0007565 female pregnancy
• GO:0019441 tryptophan catabolic process to kynurenine
• GO:0019805 quinolinate biosynthetic process
• GO:0032496 response to lipopolysaccharide
• GO:0032693 negative regulation of interleukin-10 production
• GO:0032735 positive regulation of interleukin-12 production
• GO:0033555 multicellular organismal response to stress
• GO:0034276 kynurenic acid biosynthetic process
• GO:0034354 'de novo' NAD biosynthetic process from tryptophan
• GO:0036269 swimming behavior
• GO:0042098 T cell proliferation
• GO:0042130 negative regulation of T cell proliferation
• GO:0043065 positive regulation of apoptotic process
• GO:0046006 regulation of activated T cell proliferation
• GO:0070233 negative regulation of T cell apoptotic process
• GO:0070234 positive regulation of T cell apoptotic process

Cellular Component

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0030485 smooth muscle contractile fiber
• GO:0032421 stereocilium bundle

External links

• PDB: RCSB:5ek3, PDBe:5ek3, PDBj:5ek3
• PDBsum: 5ek3
• PubMed: 26642377
• UniProt: P14902|I23O1_HUMAN Indoleamine 2,3-dioxygenase 1 (Gene Name=IDO1)