Structural modifications of the Ω loop in human acetylcholinesterase

FEBS Letters

Shafferman, Avigdor¹  Ariel, Naomi¹  Leitner, Moshe¹  Ordentlich, Arie¹  Barak, Dov²  Velan, Baruch¹  Bino, Tamar¹ 

[1]Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 70450, Israel

[2]Department of Organic Chemistry, Israel Institute for Biological Research, Ness-Ziona 70450, Israel

关键词: Acetylcholinesterase;    Ω loop;    Mutagenesis;    Deletion;    Allosteric effect;   

DOI  :  10.1016/0014-5793(96)00995-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Conformational mobility of the surface Ω loop (Cys-69-Cys-96) in human acetylcholinesterase (HuAChE) was recently implicated in substrate accessibility to the active center and in the mechanism of allosteric modulation of enzymatic activity. We therefore generated and kinetically evaluated the following modifications or replacements in HuAChE: (a) residues at the loop ends, (b) residues involved in putative hydrogen-bond interactions within the loop and between the loop and the protein core, (c) ChEs conserved proline residues within the loop and (d) a deletion of a conserved segment of 5 residues. All the residue replacements, including those of the prolines, had either limited or no effect on enzyme reactivity. These results suggest that unlike the case of lipase, the Ω loop in the HuAChE is not involved in large lid-like displacements. In cases where modifications of the loop sequence had some effect on reactivity, the effects could be attributed to an altered position of residue Trp-86 supporting the proposed coupling between the structure of the Ω loop and the positioning of the Trp-86 indole moiety, in catalytic activity and in allosterism.

【 授权许可】

Unknown