Journal
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Volume 41, Issue 18, Pages 8831-8843Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2022.2137699
Keywords
Anti-inflammatory; Serratiopeptidase; N412D; In-silico mutagenesis; Electrostatic potential
Categories
Ask authors/readers for more resources
This study aimed to enhance the acid resistance of Serratiopeptidase through computational interventions. The N412D mutant was identified as the most stable mutant with negative electrostatic potential, which can stabilize Serratiopeptidase amid extreme pH values.
Serratiopeptidase is the multifunctionality metalloendopeptidase extensively employed in biopharmaceutical and industrial biotechnology. Despite its poor pH tolerance, serratiopeptidase must withstand the highly acidic environment of the gastrointestinal tract to be used as a potent anti-inflammatory and analgesic medication. In earlier studies, post-translational deamination related mutations showed alteration in the net charge of protein's surface. Therefore, the current study aimed to enhance the acid resistance of serratiopeptidase via implementing computational interventions to screen out the most stable mutational hotspot. The methodology used in this study is as follows: (a) Higher accessibility to surface (b) 4 angstrom away from active site region to avoid interference with its proteolytic activity, and (c) By converting non-conserved amide residues to acidic residues. A docking study has been conducted to establish the substrate specificity and binding affinity to native and mutant proteins. The docking outcomes were then validated using molecular dynamic simulations to clarify each mutant's molecular stability and conformation while preserving their activity. The results showed that N412D is the best-screened mutant with negative electrostatic potential that can alter the overall charge on the protein's surface with increased H+ ions. Alteration in overall charge leads to protein surface more acidic that causes a common ion effect in stomach pH and act as a buffer which could stabilize the serratiopeptidase amid extreme pH. Communicated by Ramaswamy H. Sarma
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available