Structure of PDB 2dr0 Chain A Binding Site BS02

Receptor Information

>2dr0 Chain A (length=532) Species: 9606 (Homo sapiens)

SSPPVVDTVHGKVLGKFVSLEGFAQPVAIFLGIPFAKPPLGPLRFTPPQP
AEPWSFVKNATSYPPMCTQDPKAGQLLSELFTNRKENIPLKLSEDCLYLN
IYTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQY
RLGIWGFFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGE
SAGGESVSVLVLSPLAKNLFHRAISESGVALTSVLVKKGDVKPLAEQIAI
TAGCKTTTSAVMVHCLRQKTEEELLETTLKMKFLSLDLQGDPRESQPLLG
TVIDGMLLLKTPEELQAERNFHTVPYMVGINKQEFGWLIPMLMSYPLSEG
QLDQKTAMSLLWKSYPLVCIAKELIPEATEKYLGGTDDTVKKKDLFLDLI
ADVMFGVPSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDE
LFSVFGAPFLKEGASEEEIRLSKMVMKFWANFARNGNPNGEGLPHWPEYN
QKEGYLQIGANTQAAQKLKDKEVAFWTNLFAK

Ligand information

• Ligand ID: TCH
• InChI: InChI=1S/C26H45NO7S/c1-15(4-7-23(31)27-10-11-35(32,33)34)18-5-6-19-24-20(14-22(30)26(18,19)3)25(2)9-8-17(28)12-16(25)13-21(24)29/h15-22,24,28-30H,4-14H2,1-3H3,(H,27,31)(H,32,33,34)/t15-,16+,17-,18-,19+,20+,21-,22+,24+,25+,26-/m1/s1
• InChIKey: WBWWGRHZICKQGZ-HZAMXZRMSA-N
• SMILES:
  OpenEye OEToolkits 1.7.2: CC(CCC(=O)NCCS(=O)(=O)O)C1CCC2C1(C(CC3C2C(CC4C3(CCC(C4)O)C)O)O)C
  ACDLabs 12.01: O=S(=O)(O)CCNC(=O)CCC(C3CCC2C1C(O)CC4CC(O)CCC4(C)C1CC(O)C23C)C
  CACTVS 3.370: C[C@H](CCC(=O)NCC[S](O)(=O)=O)[C@H]1CC[C@H]2[C@@H]3[C@H](O)C[C@@H]4C[C@H](O)CC[C@]4(C)[C@H]3C[C@H](O)[C@]12C
  CACTVS 3.370: C[CH](CCC(=O)NCC[S](O)(=O)=O)[CH]1CC[CH]2[CH]3[CH](O)C[CH]4C[CH](O)CC[C]4(C)[CH]3C[CH](O)[C]12C
  OpenEye OEToolkits 1.7.2: C[C@H](CCC(=O)NCCS(=O)(=O)O)[C@H]1CC[C@@H]2[C@@]1([C@H](C[C@H]3[C@H]2[C@@H](C[C@H]4[C@@]3(CC[C@H](C4)O)C)O)O)C
• Formula: C26 H45 N O7 S
• Name: TAUROCHOLIC ACID
• ChEMBL: CHEMBL224867
• DrugBank: DB04348
• ZINC: ZINC000008214684
• PDB chain: 2dr0 Chain A Residue 101

Receptor-Ligand Complex Structure

Structure summary

• PDB: 2dr0 Multisite promiscuity in the processing of endogenous substrates by human carboxylesterase 1
• Resolution: 3.2 Å
• Binding residue (original residue number in PDB): L1368 S1369 G1371 K1414
• Binding residue (residue number reindexed from 1): L347 S348 G350 K393
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): G1142 G1143 S1221 A1222 E1354 H1468
• Catalytic site (residue number reindexed from 1): G122 G123 S201 A202 E334 H447
• Enzyme Commision number: 3.1.1.1: carboxylesterase.
  3.1.1.13: sterol esterase.
  3.1.1.56: methylumbelliferyl-acetate deacetylase.

Gene Ontology

Molecular Function

• GO:0004771 sterol ester esterase activity
• GO:0047374 methylumbelliferyl-acetate deacetylase activity
• GO:0052689 carboxylic ester hydrolase activity
• GO:0106435 carboxylesterase activity

Biological Process

• GO:0006629 lipid metabolic process
• GO:0006695 cholesterol biosynthetic process
• GO:0008203 cholesterol metabolic process
• GO:0009636 response to toxic substance
• GO:0010875 positive regulation of cholesterol efflux
• GO:0010887 negative regulation of cholesterol storage
• GO:0016042 lipid catabolic process
• GO:0030855 epithelial cell differentiation
• GO:0042632 cholesterol homeostasis
• GO:0043691 reverse cholesterol transport
• GO:0051791 medium-chain fatty acid metabolic process
• GO:0070857 regulation of bile acid biosynthetic process
• GO:0071397 cellular response to cholesterol
• GO:0071404 cellular response to low-density lipoprotein particle stimulus
• GO:0090122 cholesterol ester hydrolysis involved in cholesterol transport
• GO:0090205 positive regulation of cholesterol metabolic process
• GO:0120188 regulation of bile acid secretion

Cellular Component

• GO:0005737 cytoplasm
• GO:0005783 endoplasmic reticulum
• GO:0005788 endoplasmic reticulum lumen
• GO:0005811 lipid droplet
• GO:0005829 cytosol

External links

• PDB: RCSB:2dr0, PDBe:2dr0, PDBj:2dr0
• PDBsum: 2dr0
• PubMed: 16962139
• UniProt: P23141|EST1_HUMAN Liver carboxylesterase 1 (Gene Name=CES1)