Site- selective peptide bond hydrolysis and ligation in water by short peptide- based assemblies

• 成果类型: Article
• 署名作者: Singh, Abhishek; Chakraborty, Janardan; Pal, Sumit; Das, Dibyendu
• 署名单位: Indian Institute of Science Education & Research (IISER) - Kolkata; Indian Institute of Science Education & Research (IISER) - Kolkata
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-12572
• DOI: 10.1073/pnas.2321396121
• 发表日期: 2024-07-30
• 关键词: systems chemistry; ACID; protein; prions; LIFE; EVOLUTION; catalysis; origins; complex

摘要

The evolution of complex chemical inventory from Darwin's nutrient- rich warm pond necessitated rudimentary yet efficient catalytic folds. Short peptides and their self- organized microstructures, ranging from spherical colloids to amyloidogenic aggregates might have played a crucial role in the emergence of contemporary catalytic entities. However, the question of how short peptide fragments had functions akin to contemporary complex enzymes to catalyze cleavage and formation of highly stable peptide bonds that constitute the backbone of all proteins remains an unresolved yet fundamentally important question in terms of the origins of enzymes. We report short- peptide- based spherical assemblies that demonstrated residue- specific cleavage and formation of peptide bonds of diverse peptide- based substrates under aqueous environment. Despite the short sequence length, the assemblies utilized the synergistic collaboration of four residues which included the catalytic triad of extant serine proteases with a nonproteinogenic amino acid (quinone moiety), to facilitate proteolysis, ligation, and a three- step (hydrolysis-ligation-hydrolysis) cascade. Such short- peptide- based catalytic assemblies argue for their candidacy as the earliest protein folds and open up avenues for biotechnological applications.