Ester hydrolysis is of wide biomedical interest, spanning from the green synthesis of pharmaceuticals to biomaterials' development. Existing peptide-based catalysts exhibit low catalytic efficiency compared to natural enzymes, due to the conformational heterogeneity of peptides. Moreover, there is lack of understanding of the correlation between the primary sequence and catalytic function. For this purpose, we statistically analyzed 22 EC 3.1 hydrolases with known catalytic triads, characterized by unique and well-defined mechanisms. The aim was to identify patterns at the sequence level that will better inform the creation of short peptides containing important information for catalysis, based on the catalytic triad, oxyanion holes and the triad residues microenvironments. Moreover, fragmentation schemes of the primary sequence of selected enzymes alongside the study of their amino acid frequencies, composition, and physicochemical properties are proposed. The results showed highly conserved catalytic sites with distinct positional patterns and chemical microenvironments that favor catalysis and revealed variations in catalytic site composition that could be useful for the design of minimalistic catalysts.

Esterase Sequence Composition Patterns for the Identification of Catalytic Triad Microenvironment Motifs

Marchesan, Silvia;
2022-01-01

Abstract

Ester hydrolysis is of wide biomedical interest, spanning from the green synthesis of pharmaceuticals to biomaterials' development. Existing peptide-based catalysts exhibit low catalytic efficiency compared to natural enzymes, due to the conformational heterogeneity of peptides. Moreover, there is lack of understanding of the correlation between the primary sequence and catalytic function. For this purpose, we statistically analyzed 22 EC 3.1 hydrolases with known catalytic triads, characterized by unique and well-defined mechanisms. The aim was to identify patterns at the sequence level that will better inform the creation of short peptides containing important information for catalysis, based on the catalytic triad, oxyanion holes and the triad residues microenvironments. Moreover, fragmentation schemes of the primary sequence of selected enzymes alongside the study of their amino acid frequencies, composition, and physicochemical properties are proposed. The results showed highly conserved catalytic sites with distinct positional patterns and chemical microenvironments that favor catalysis and revealed variations in catalytic site composition that could be useful for the design of minimalistic catalysts.
File in questo prodotto:
File Dimensione Formato  
acs.jcim.2c00977.pdf

Accesso chiuso

Descrizione: pdf editoriale
Tipologia: Documento in Versione Editoriale
Licenza: Copyright dell'editore
Dimensione 6.13 MB
Formato Adobe PDF
6.13 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
ci2c00977_si_001.pdf

Accesso chiuso

Descrizione: supplementary material
Tipologia: Altro materiale allegato
Licenza: Copyright Editore
Dimensione 6.84 MB
Formato Adobe PDF
6.84 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
acs.jcim.2c00977-Post_print.pdf

Open Access dal 13/10/2023

Tipologia: Bozza finale post-referaggio (post-print)
Licenza: Digital Rights Management non definito
Dimensione 6.07 MB
Formato Adobe PDF
6.07 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11368/3037179
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 5
social impact