Why is binding of a divalent metal cation to a structural motif containing four carboxylate residues not accompanied by a conformational change?

Autor: Lushchekina S; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel., Weiner L; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel.; Department of Chemical Research Support, Weizmann Institute of Science, Rehovot, Israel., Ashani Y; Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel., Emrizal R; Department of Applied Physics, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Malaysia., Firdaus-Raih M; Department of Applied Physics, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, Bangi, Malaysia.; Institute of Systems Biology, Universiti Kebangsaan Malaysia, Bangi, Malaysia., Silman I; Department of Brain Sciences, Weizmann Institute of Science, Rehovot, Israel., Sussman JL; Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot, Israel.; Structural Proteomics Unit, Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel.
Jazyk: angličtina
Zdroj: Protein science : a publication of the Protein Society [Protein Sci] 2024 Dec; Vol. 33 (12), pp. e5206.
DOI: 10.1002/pro.5206
Abstrakt: We earlier showed that Torpedo californica acetylcholinesterase (AChE) contains a cluster of four conserved aspartates that can strongly bind divalent cations, which we named the 4D motif. Binding of the divalent metal cations greatly increases its thermal stability. Here we systematically examined all available crystallographic structures of T. californica AChE. Two additional metal-binding sites were identified, both composed of acidic and histidine residues. Relative binding to the 4D and additional sites was studied using metadynamics simulations. It was observed that in crystal structures devoid of metal ions in the 4D site, the conformation of T. californica AChE is almost identical to that in structures in which it is occupied by a divalent metal ion. Closer examination of the 4D motif reveals that three of the four acidic residues form ion pairs with conserved basic residues surrounding them. We named this new motif the 4A/3B motif. Molecular dynamics with quantum potential simulations was used to quantify the 4D motif's binding strength compared with that of the metal-binding site in the protein fXIIIa, which consists of four aspartates, but is devoid of adjacent cationic residues. Whereas fXIIIa's 4D site, in the absence of a metal cation, expanded significantly in the simulation, that of Torpedo AChE displayed only minor periodic changes in size. Furthermore, the energy of metal ion unbinding from the two sites differs by ca. 10 kcal/mol. We identified several other proteins in the PDB that contain the 4A/3B motif, whose conformations are identical in the presence or absence of a metal ion. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at https://proteopedia.org/w/Journal:Protein_Science:4.
(© 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.)
Databáze: MEDLINE
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