TY - JOUR
T1 - Exploring the Esterase Catalytic Activity of Minimalist Heptapeptide Amyloid Fibers
AU - Roldán-Martín, Lorena
AU - Rodríguez Santiago, Luis
AU - Maréchal, Jean-Didier
AU - Sodupe Roure, Mariona
PY - 2024/9/5
Y1 - 2024/9/5
N2 - This paper investigates the esterase activity of minimalist amyloid fibers composed of short seven-residue peptides, IHIHIHI (IH7) and IHIHIQI (IH7Q), with a particular focus on the role of the sixth residue position within the peptide sequence. Through computational simulations and analyses, we explore the molecular mechanisms underlying catalysis in these amyloid-based enzymes. Contrary to initial hypotheses, our study reveals that the twist angle of the fiber, and thus the catalytic site's environment, is not notably affected by the sixth residue. Instead, the sixth residue interacts with the p-nitrophenylacetate (pNPA) substrate, particularly through its −NO group, potentially enhancing catalysis. Quantum mechanics/molecular mechanics (QM/MM) simulations of the reaction mechanism suggest that the polarizing effect of glutamine enhances catalytic activity by forming a stabilizing network of hydrogen bonds with pNPA, leading to lower energy barriers and a more exergonic reaction. Our findings provide valuable insights into the intricate interplay between peptide sequence, structural arrangement, and catalytic function in amyloid-based enzymes, offering potentially valuable information for the design and optimization of biomimetic catalysts.
AB - This paper investigates the esterase activity of minimalist amyloid fibers composed of short seven-residue peptides, IHIHIHI (IH7) and IHIHIQI (IH7Q), with a particular focus on the role of the sixth residue position within the peptide sequence. Through computational simulations and analyses, we explore the molecular mechanisms underlying catalysis in these amyloid-based enzymes. Contrary to initial hypotheses, our study reveals that the twist angle of the fiber, and thus the catalytic site's environment, is not notably affected by the sixth residue. Instead, the sixth residue interacts with the p-nitrophenylacetate (pNPA) substrate, particularly through its −NO group, potentially enhancing catalysis. Quantum mechanics/molecular mechanics (QM/MM) simulations of the reaction mechanism suggest that the polarizing effect of glutamine enhances catalytic activity by forming a stabilizing network of hydrogen bonds with pNPA, leading to lower energy barriers and a more exergonic reaction. Our findings provide valuable insights into the intricate interplay between peptide sequence, structural arrangement, and catalytic function in amyloid-based enzymes, offering potentially valuable information for the design and optimization of biomimetic catalysts.
KW - Amyloid fibers
KW - Catalysis
KW - Dft
KW - Esterase activity
KW - Qm/mm
UR - http://www.scopus.com/inward/record.url?scp=85201533067&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/6a71e543-832f-3984-8d6d-32e80ee90c34/
U2 - 10.1002/chem.202401797
DO - 10.1002/chem.202401797
M3 - Article
C2 - 38973291
SN - 1521-3765
VL - 30
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 50
M1 - e202401797
ER -