Computational study on the polymerization reaction of d-aminopeptidase for the synthesis of d-peptides
| Autor: | Keiji Numata, Yasuhisa Asano, Ayaka Tateishi, Takanori Kigawa, Joan Gimenez-Dejoz, Kousuke Tsuchiya, Yoko Motoda |
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| Rok vydání: | 2020 |
| Předmět: |
0303 health sciences
Proteases General Chemical Engineering General Chemistry 010402 general chemistry 01 natural sciences Combinatorial chemistry Aminopeptidase 0104 chemical sciences Acylation 03 medical and health sciences chemistry.chemical_compound Stereospecificity Aminolysis chemistry Polymerization Peptide synthesis Chirality (chemistry) 030304 developmental biology |
| Zdroj: | RSC advances. 10(30) |
| ISSN: | 2046-2069 |
| Popis: | Almost all natural proteins are composed exclusively of L-amino acids, and this chirality influences their properties, functions, and selectivity. Proteases can recognize proteins composed of L-amino acids but display lower selectivity for their stereoisomers, D-amino acids. Taking this as an advantage, D-amino acids can be used to develop polypeptides or biobased materials with higher biostability. Chemoenzymatic peptide synthesis is a technique that uses proteases as biocatalysts to synthesize polypeptides, and D-stereospecific proteases can be used to synthesize polypeptides incorporating D-amino acids. However, engineered proteases with modified catalytic activities are required to allow the incorporation of D-amino acids with increased efficiency. To understand the stereospecificity presented by proteases and their involvement in polymerization reactions, we studied D-aminopeptidase. This enzyme displays the ability to efficiently synthesize poly D-alanine-based peptides under mild conditions. To elucidate the mechanisms involved in the unique specificity of D-aminopeptidase, we performed quantum mechanics/molecular mechanics simulations of its polymerization reaction and determined the energy barriers presented by the chiral substrates. The enzyme faces higher activation barriers for the acylation and aminolysis reactions with the L-stereoisomer than with the D-substrate (10.7 and 17.7 kcal mol−1 higher, respectively). The simulation results suggest that changes in the interaction of the substrate with Asn155 influence the stereospecificity of the polymerization reaction. |
| Databáze: | OpenAIRE |
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