Glucose oxidase from Penicillium amagasakiense: Characterization of the transition state of its denaturation from molecular dynamics simulations
2014 (English)In: Proteins: Structure, Function, and Genetics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 82, no 10, 2353-2363 p.Article in journal (Refereed) Published
Glucose oxidase (GOx) is a flavoenzyme having applications in food and medical industries. However, GOx, as many other enzymes when extracted from the cells, has relatively short operational lifetimes. Several recent studies (both experimental and theoretical), carried out on small proteins (or small fractions of large proteins), show that a detailed knowledge of how the breakdown process starts and proceeds on molecular level could be of significant help to artificially improve the stability of fragile proteins. We have performed extended molecular dynamics (MD) simulations to study the denaturation of GOx (a protein dimer containing nearly 1200 amino acids) to identify weak points in its structure and in this way gather information to later make it more stable, for example, by mutations. A denaturation of a protein can be simulated by increasing the temperature far above physiological temperature. We have performed a series of MD simulations at different temperatures (300, 400, 500, and 600 K). The exit from the protein's native state has been successfully identified with the clustering method and supported by other methods used to analyze the simulation data. A common set of amino acids is regularly found to initiate the denaturation, suggesting a moiety where the enzyme could be strengthened by a suitable amino acid based modification.
Place, publisher, year, edition, pages
2014. Vol. 82, no 10, 2353-2363 p.
protein denaturation, mutation, unfolding, MD simulation, cluster analysis
Biochemistry and Molecular Biology Biophysics Chemical Sciences
Research subject Physical Chemistry
IdentifiersURN: urn:nbn:se:su:diva-109018DOI: 10.1002/prot.24596ISI: 000342849400006OAI: oai:DiVA.org:su-109018DiVA: diva2:778171