1MX1

Crystal Structure of Human Liver Carboxylesterase in complex with tacrine

1MX1 の概要

• エントリーDOI: 10.2210/pdb1mx1/pdb
• 関連するPDBエントリー: 1MX5 1MX9
• 分子名称: liver Carboxylesterase I, 2-acetamido-2-deoxy-alpha-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• 機能のキーワード: esterase, hydrolase, esterase inhibitor
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 367246.28

構造登録者

Bencharit, S.,Morton, C.L.,Hyatt, J.L.,Kuhn, P.,Danks, M.K.,Potter, P.M.,Redinbo, M.R. (登録日: 2002-10-01, 公開日: 2003-04-22, 最終更新日: 2024-12-25)

主引用文献

Bencharit, S.,Morton, C.L.,Hyatt, J.L.,Kuhn, P.,Danks, M.K.,Potter, P.M.,Redinbo, M.R.
Crystal Structure of Human Carboxylesterase 1 Complexed with the Alzheimer's Drug Tacrine: From Binding Promiscuity to Selective Inhibition
CHEM.BIOL., 10:341-349, 2003

PubMed Abstract: Human carboxylesterase 1 (hCE1) is a broad-spectrum bioscavenger that plays important roles in narcotic metabolism, clinical prodrug activation, and the processing of fatty acid and cholesterol derivatives. We determined the 2.4 A crystal structure of hCE1 in complex with tacrine, the first drug approved for treating Alzheimer's disease, and compare this structure to the Torpedo californica acetylcholinesterase (AcChE)-tacrine complex. Tacrine binds in multiple orientations within the catalytic gorge of hCE1, while it stacks in the smaller AcChE active site between aromatic side chains. Our results show that hCE1's promiscuous action on distinct substrates is enhanced by its ability to interact with ligands in multiple orientations at once. Further, we use our structure to identify tacrine derivatives that act as low-micromolar inhibitors of hCE1 and may provide new avenues for treating narcotic abuse and cholesterol-related diseases.

PubMed: 12725862
DOI: 10.1016/S1074-5521(03)00071-1

実験手法

X-RAY DIFFRACTION (2.4 Å)