Title : Crystallization and X-ray structure of full-length recombinant human
butyrylcholinesterase
Abstract :
- Human butyrylcholinesterase ( BChE ) has been shown to function as an endogenous scavenger of diverse poisons
- BChE is a 340 kDa tetrameric glycoprotein that is present in human serum at a concentration of 5 mg l(-1 )
- The well documented therapeutic effects of BChE on cocaine toxicity and organophosphorus agent poisoning has increased the need for effective methods of producing recombinant therapeutic BChE
- In order to be therapeutically useful, BChE must have a long circulatory residence time or associate as tetramers
- Full-length recombinant BChE produced in Chinese hamster ovary (CHO) cells or human embryonic kidney cells has been shown to associate as monomers, with a shorter circulatory residence time than the naturally occurring tetrameric serum protein
- Based on the preceding observation as well as the need to develop novel methodologies to facilitate the mass production of therapeutic recombinant BChE , studies have been initiated to determine the structural basis of tetramer formation
- Towards these ends, full-length monomeric recombinant BChE has been crystallized for the first time
- A 2.8 A X-ray structure was solved in space group P42 ( 1)2 , with unit-cell parameters a = b = 156, c = 146 A