Silman_2021_Protein.Sci_30_966

Reference

Title : Torpedo californica acetylcholinesterase is stabilized by binding of a divalent metal ion to a novel and versatile 4D motif - Silman_2021_Protein.Sci_30_966
Author(s) : Silman I , Shnyrov VL , Ashani Y , Roth E , Nicolas A , Sussman JL , Weiner L
Ref : Protein Science , 30 :966 , 2021
Abstract :

Stabilization of Torpedo californica acetylcholinesterase by the divalent cations Ca(+2) , Mg(+2) and Mn(+2) was investigated. All three substantially protect the enzyme from thermal inactivation. Electron paramagnetic resonance revealed one high-affinity binding site for Mn(+2) and several much weaker sites. Differential scanning calorimetry showed a single irreversible thermal transition. All three cations raise both the temperature of the transition and the activation energy, with the transition becoming more cooperative. The crystal structures of the Ca(+2) and Mg(+2) complexes with Torpedo acetylcholinesterase were solved. A principal binding site was identified. In both cases, it consists of four aspartates (a 4D motif), within which the divalent ion is embedded, together with several waters molecules. It makes direct contact with two of the aspartates, and indirect contact, via waters, with the other two. The 4D motif has been identified in 31 acetylcholinesterase sequences and 28 butyrylcholinesterase sequences. Zebrafish acetylcholinesterase also contains the 4D motif; it, too, is stabilized by divalent metal ions. The ASSAM server retrieved 200 other proteins that display the 4D motif, in many of which it is occupied by a divalent cation. It is a very versatile motif, since, even though tightly conserved in terms of rmsd values, it can contain from one to as many as three divalent metal ions, together with a variable number of waters. This novel motif, which binds primarily divalent metal ions, is shared by a broad repertoire of proteins. This article is protected by copyright. All rights reserved.

PubMedSearch : Silman_2021_Protein.Sci_30_966
PubMedID: 33686648
Gene_locus related to this paper: torca-ACHE

Related information

Gene_locus torca-ACHE
Structure 7B38    7B8E    7B2W

Citations formats

Silman I, Shnyrov VL, Ashani Y, Roth E, Nicolas A, Sussman JL, Weiner L (2021)
Torpedo californica acetylcholinesterase is stabilized by binding of a divalent metal ion to a novel and versatile 4D motif
Protein Science 30 :966

Silman I, Shnyrov VL, Ashani Y, Roth E, Nicolas A, Sussman JL, Weiner L (2021)
Protein Science 30 :966