Harel_2005_Chem.Biol.Interact_157-158_153

Reference

Title : The 3D structure of the anticancer prodrug CPT-11 with Torpedo californica acetylcholinesterase rationalizes its inhibitory action on AChE and its hydrolysis by butyrylcholinesterase and carboxylesterase - Harel_2005_Chem.Biol.Interact_157-158_153
Author(s) : Harel M , Hyatt JL , Brumshtein B , Morton CL , Wadkins RM , Silman I , Sussman JL , Potter PM
Ref : Chemico-Biological Interactions , 157-158 :153 , 2005
Abstract :

The anticancer prodrug CPT-11 is a highly effective camptothecin analog that has been approved for the treatment of colon cancer. The 2.6 angstroms resolution crystal structure of its complex with Torpedo californica acetylcholinesterase (TcAChE) demonstrates that CPT-11 binds to TcAChE and spans its gorge similarly to the Alzheimer drug, Aricept. The crystal structure clearly reveals the interactions, which contribute to the inhibitory action of CPT-11. Modeling of the complexes of CPT-11 with mammalian butyrylcholinesterase and carboxylesterase, both of which are known to hydrolyze the drug, shows how binding to either of the two enzymes yields a productive substrate-enzyme complex.

PubMedSearch : Harel_2005_Chem.Biol.Interact_157-158_153
PubMedID: 16289500
Gene_locus related to this paper: torca-ACHE

Related information

Inhibitor Irinotecan
Gene_locus Irinotecan    torca-ACHE
Structure Irinotecan    torca-ACHE    1U65

Citations formats

Harel M, Hyatt JL, Brumshtein B, Morton CL, Wadkins RM, Silman I, Sussman JL, Potter PM (2005)
The 3D structure of the anticancer prodrug CPT-11 with Torpedo californica acetylcholinesterase rationalizes its inhibitory action on AChE and its hydrolysis by butyrylcholinesterase and carboxylesterase
Chemico-Biological Interactions 157-158 :153

Harel M, Hyatt JL, Brumshtein B, Morton CL, Wadkins RM, Silman I, Sussman JL, Potter PM (2005)
Chemico-Biological Interactions 157-158 :153