Structure of PDB 2hrr Chain B Binding Site BS03

Receptor Information

>2hrr Chain B (length=531) Species: 9606 (Homo sapiens)

SPPVVDTVHGKVLGKFVSLEGFAQPVAIFLGIPFAKPPLGPLRFTPPQPA
EPWSFVKNATSYPPMCTQDPKAGQLLSELFTNRKENIPLKLSEDCLYLNI
YTPADLTKKNRLPVMVWIHGGGLMVGAASTYDGLALAAHENVVVVTIQYR
LGIWGFFSTGDEHSRGNWGHLDQVAALRWVQDNIASFGGNPGSVTIFGES
AGGESVSVLVLSPLAKNLFHRAISESGVALTSVLVKKGDVKPLAEQIAIT
AGCKTTTSAVMVHCLRQKTEEELLETTLKMKFLSLDLQGDPRESQPLLGT
VIDGMLLLKTPEELQAERNFHTVPYMVGINKQEFGWLIPMLMSYPLSEGQ
LDQKTAMSLLWKSYPLVCIAKELIPEATEKYLGGTDDTVKKKDLFLDLIA
DVMFGVPSVIVARNHRDAGAPTYMYEFQYRPSFSSDMKPKTVIGDHGDEL
FSVFGAPFLKEGASEEEIRLSKMVMKFWANFARNGNPNGEGLPHWPEYNQ
KEGYLQIGANTQAAQKLKDKEVAFWTNLFAK

Ligand information

• Ligand ID: SIA
• InChI: InChI=1S/C11H19NO9/c1-4(14)12-7-5(15)2-11(20,10(18)19)21-9(7)8(17)6(16)3-13/h5-9,13,15-17,20H,2-3H2,1H3,(H,12,14)(H,18,19)/t5-,6+,7+,8+,9+,11+/m0/s1
• InChIKey: SQVRNKJHWKZAKO-YRMXFSIDSA-N
• SMILES:
  CACTVS 3.341: CC(=O)N[CH]1[CH](O)C[C](O)(O[CH]1[CH](O)[CH](O)CO)C(O)=O
  OpenEye OEToolkits 1.5.0: CC(=O)NC1C(CC(OC1C(C(CO)O)O)(C(=O)O)O)O
  OpenEye OEToolkits 1.5.0: CC(=O)N[C@@H]1[C@H](C[C@@](O[C@H]1[C@@H]([C@@H](CO)O)O)(C(=O)O)O)O
  ACDLabs 10.04: O=C(O)C1(O)OC(C(O)C(O)CO)C(NC(=O)C)C(O)C1
  CACTVS 3.341: CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(O[C@H]1[C@H](O)[C@H](O)CO)C(O)=O
• Formula: C11 H19 N O9
• Name: N-acetyl-alpha-neuraminic acid;
  N-acetylneuraminic acid;
  sialic acid;
  alpha-sialic acid;
  O-SIALIC ACID
• ChEMBL: CHEMBL1234621
• DrugBank: DB03721
• ZINC: ZINC000004081651
• PDB chain: 2hrr Chain B Residue 282

Receptor-Ligand Complex Structure

Structure summary

• PDB: 2hrr Crystal Structures of Human Carboxylesterase 1 in Covalent Complexes with the Chemical Warfare Agents Soman and Tabun.
• Resolution: 2.7 Å
• Binding residue (original residue number in PDB): G2052 K2078 N2079 S2082 P2084
• Binding residue (residue number reindexed from 1): G31 K57 N58 S61 P63
• Annotation score: 1

Enzymatic activity

• Catalytic site (original residue number in PDB): G2142 G2143 S2221 A2222 E2354 H2468
• Catalytic site (residue number reindexed from 1): G121 G122 S200 A201 E333 H446
• 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:2hrr, PDBe:2hrr, PDBj:2hrr
• PDBsum: 2hrr
• PubMed: 17407327
• UniProt: P23141|EST1_HUMAN Liver carboxylesterase 1 (Gene Name=CES1)