ArticlePloS one2014
Computational design of a pH stable enzyme: understanding molecular mechanism of penicillin acylase's adaptation to alkaline conditions.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Exploration of Alkaliphilic Bacteria Alkalitalea saponilacus Identifies Glycoside Hydrolases With Biotechnological Potential.Microbial biotechnology · 2026Article
- Mitigating alkaline instability induced by tyrosine-tyrosine repulsion in an FcγRIIIa-binding protein through phenylalanine substitution.Journal of biochemistry · 2026Article
- Production and Applications of Cyanobacterial Phycocyanin: Trends and Prospects.Indian journal of microbiology · 2025Article
- A Deep Retrieval-Enhanced Meta-Learning Framework for Enzyme Optimum pH Prediction.Journal of chemical information and modeling · 2025Article
- Accurately predicting optimal conditions for microorganism proteins through geometric graph learning and language model.Communications biology · 2024Article
- Mining and rational design of psychrophilic catalases using metagenomics and deep learning models.Applied microbiology and biotechnology · 2024Article
- Exploring the Structurally Conserved Regions and Functional Significance in Bacterial N-Terminal Nucleophile (Ntn) Amide-Hydrolases.International journal of molecular sciences · 2024Article
- Advances in recombinant protease production: current state and perspectives.World journal of microbiology & biotechnology · 2024Review
- Living in trinity of extremes: Genomic and proteomic signatures of halophilic, thermophilic, and pH adaptation.Current research in structural biology · 2024Article
- A Hydrolase Produced byToxins · 2023Article
- Acid-resistant enzymes: the acquisition strategies and applications.Applied microbiology and biotechnology · 2023Review
- A Brief History of Colour, the Environmental Impact of Synthetic Dyes and Removal by Using Laccases.Molecules (Basel, Switzerland) · 2021Review
- Recombinant laccase rPOXA 1B real-time, accelerated and molecular dynamics stability study.BMC biotechnology · 2021Article
- Zebra2: advanced and easy-to-use web-server for bioinformatic analysis of subfamily-specific and conserved positions in diverse protein superfamilies.Nucleic acids research · 2020Article
- Multifactorial level of extremostability of proteins: can they be exploited for protein engineering?Extremophiles : life under extreme conditions · 2017Review
- Insights from molecular dynamics simulations for computational protein design.Molecular systems design & engineering · 2017Article
- Rapid enzyme regeneration results in the striking catalytic longevity of an engineered, single species, biocatalytic biofilm.Microbial cell factories · 2016Article
- Sequence and structure-based comparative analysis to assess, identify and improve the thermostability of penicillin G acylases.Journal of industrial microbiology & biotechnology · 2015Article
- Engineering protocells: prospects for self-assembly and nanoscale production-lines.Life (Basel, Switzerland) · 2015Review
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6 authors.
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Abstract
Protein stability provides advantageous development of novel properties and can be crucial in affording tolerance to mutations that introduce functionally preferential phenotypes. Consequently, understanding the determining factors for protein stability is important for the study of structure-function relationship and design of novel protein functions. Thermal stability has been extensively studied in connection with practical application of biocatalysts. However, little work has been done to explore the mechanism of pH-dependent inactivation. In this study, bioinformatic analysis of the Ntn-hydrolase superfamily was performed to identify functionally important subfamily-specific positions in protein structures. Furthermore, the involvement of these positions in pH-induced inactivation was studied. The conformational mobility of penicillin acylase in Escherichia coli was analyzed through molecular modeling in neutral and alkaline conditions. Two functionally important subfamily-specific residues, Gluβ482 and Aspβ484, were found. Ionization of these residues at alkaline pH promoted the collapse of a buried network of stabilizing interactions that consequently disrupted the functional protein conformation. The subfamily-specific position Aspβ484 was selected as a hotspot for mutation to engineer enzyme variant tolerant to alkaline medium. The corresponding Dβ484N mutant was produced and showed 9-fold increase in stability at alkaline conditions. Bioinformatic analysis of subfamily-specific positions can be further explored to study mechanisms of protein inactivation and to design more stable variants for the engineering of homologous Ntn-hydrolases with improved catalytic properties.
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