Molecular Dynamic Study on the Structure and Thermal Stability of Mutant Pediocin PA-1 Peptides Engineered with Cysteine Substitutions
© 2024. The Author(s)..
Pediocin and analogous bacteriocins, valued for thermal stability, serve as versatile antimicrobials in the food sector. Improving their resilience at high temperatures and deriving derivatives not only benefit food production but also offer broad-spectrum antimicrobial potential in pharmaceuticals, spanning treatments for peptic ulcers, women's health, and novel anticancer agents. The study aims to create mutant peptides capable of establishing a third disulfide bond or enhanced through cysteine substitutions. This involves introducing additional Cys residues into the inherent structure of pediocin PA-1 to facilitate disulfide bond formation. Five mutants (Mut 1-5) were systematically generated with double Cys substitutions and assessed for thermal stability through MD simulations across temperatures (298-394 K). The most robust mutants (Mut 1, Mut 4-5) underwent extended analysis via MD simulations, comparing their structural stability, secondary structure, and surface accessibility to the reference Pediocin PA-1 molecule. This comprehensive assessment aims to understand how Cys substitutions influence disulfide bonds and the overall thermal stability of the mutant peptides. In silico analysis indicated that Mut 1 and Mut 5, along with the reference structure, lose their helical structure and one natural disulfide bond at high temperatures, and may impacting antimicrobial activity. Conversely, Mut 4 retained its helical structure and exhibited thermal stability similar to Pediocin PA-1. Pending further experimental validation, this study implies Mut 4 may have high stability and exceptional resistance to high temperatures, potentially serving as an effective antimicrobial alternative.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
|---|---|
| Enthalten in: |
Probiotics and antimicrobial proteins - (2024) vom: 01. März |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Sevim, Büşra [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Amino acid substitutions |
|---|
| Anmerkungen: |
Date Revised 29.02.2024 published: Print-Electronic Citation Status Publisher |
|---|
| doi: |
10.1007/s12602-024-10225-3 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369142160 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369142160 | ||
| 003 | DE-627 | ||
| 005 | 20240301233259.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240301s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s12602-024-10225-3 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1313.xml |
| 035 | |a (DE-627)NLM369142160 | ||
| 035 | |a (NLM)38424320 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sevim, Büşra |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Molecular Dynamic Study on the Structure and Thermal Stability of Mutant Pediocin PA-1 Peptides Engineered with Cysteine Substitutions |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Revised 29.02.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Pediocin and analogous bacteriocins, valued for thermal stability, serve as versatile antimicrobials in the food sector. Improving their resilience at high temperatures and deriving derivatives not only benefit food production but also offer broad-spectrum antimicrobial potential in pharmaceuticals, spanning treatments for peptic ulcers, women's health, and novel anticancer agents. The study aims to create mutant peptides capable of establishing a third disulfide bond or enhanced through cysteine substitutions. This involves introducing additional Cys residues into the inherent structure of pediocin PA-1 to facilitate disulfide bond formation. Five mutants (Mut 1-5) were systematically generated with double Cys substitutions and assessed for thermal stability through MD simulations across temperatures (298-394 K). The most robust mutants (Mut 1, Mut 4-5) underwent extended analysis via MD simulations, comparing their structural stability, secondary structure, and surface accessibility to the reference Pediocin PA-1 molecule. This comprehensive assessment aims to understand how Cys substitutions influence disulfide bonds and the overall thermal stability of the mutant peptides. In silico analysis indicated that Mut 1 and Mut 5, along with the reference structure, lose their helical structure and one natural disulfide bond at high temperatures, and may impacting antimicrobial activity. Conversely, Mut 4 retained its helical structure and exhibited thermal stability similar to Pediocin PA-1. Pending further experimental validation, this study implies Mut 4 may have high stability and exceptional resistance to high temperatures, potentially serving as an effective antimicrobial alternative | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Amino acid substitutions | |
| 650 | 4 | |a Disulfide bonds | |
| 650 | 4 | |a Molecular dynamic simulations | |
| 650 | 4 | |a Pediocin PA-1 variants | |
| 650 | 4 | |a Protein engineering | |
| 650 | 4 | |a Thermal stability | |
| 700 | 1 | |a Güneş Altuntaş, Evrim |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Probiotics and antimicrobial proteins |d 2009 |g (2024) vom: 01. März |w (DE-627)NLM197266037 |x 1867-1314 |7 nnns |
| 773 | 1 | 8 | |g year:2024 |g day:01 |g month:03 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s12602-024-10225-3 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |j 2024 |b 01 |c 03 | ||