Exploring the Esterase Catalytic Activity of Minimalist Heptapeptide Amyloid Fibers
Roldán-Martín, Lorena (Universitat Autònoma de Barcelona. Departament de Química)
Rodríguez Santiago, Luis (Universitat Autònoma de Barcelona. Departament de Química)
Maréchal, Jean-Didier (Universitat Autònoma de Barcelona. Departament de Química)
Sodupe Roure, Mariona (Universitat Autònoma de Barcelona. Departament de Química)

Data:	2024
Resum:	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.
Ajuts:	Agencia Estatal de Investigación PID2020-116861GB-I00 Agencia Estatal de Investigación PID2020-112715GB-I00 Agència de Gestió d'Ajuts Universitaris i de Recerca 2020/FI_B2_01000
Nota:	Altres ajuts: acords transformatius de la UAB
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Chemistry (Weinheim), Vol. 30, Issue 50 (September 2024) , art. e202401797, ISSN 1521-3765

DOI: 10.1002/chem.202401797

7 p, 1.3 MB

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