Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative structure-function relationships (QSFR) and quantitative structure-stability relationships (QSSR) analyses are described here. The objective of these analyses is to investigate and quantitatively describe the effect of the changes in structure of protein on its function or stability. During the analysis, the structural and physico-chemical properties of the amino acid residues are related to activity or stability data derived for the group of proteins containing systematic substitutions at certain positions. Four examples of the application of these analyses on the data obtained with proteins modified by site-directed mutagenesis experiments are provided. Structure-function relationships were studied for 15 mutants in position 172 of the haloalkane dehalogenase and 19 mutants in position 222 of the subtilisin, while the structure-stability relationships were investigated for 13 mutants in position 157 of phage T4 lysozyme and 18 mutants in position 49 of alpha-subunits tryptophan synthase. A total of 402 molecular descriptors derived from AAindex database were used to quantify amino acid properties and the multivariate statistical technique--partial least squares projections to latent structures--was used to identify those of them which are important for explanation of the activity and stability data. Quantitative models were developed and internally validated for every data set. The possibilities for further development of both analyses and their application for predictive and analytical purposes in protein engineering research are discussed.
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PMID:Quantitative structure-function and structure-stability relationships of purposely modified proteins. 957 56

Non-detergent sulfobetaines (NDSB) are a family of solubilizing and stabilizing agents for proteins. In a previous study [Goldberg, M. E., Expert-Bezancon, N., Vuillard, L. & Rabilloud, T. (1996) Folding & Design 1, 21-27] we showed that the amount of active protein recovered in in vitro folding experiments could be significantly increased by some NDSBS. In this work we investigated the mechanisms by which these molecules facilitate protein renaturation. Stopped-flow and manual-mixing fluorescence and enzyme activity measurements were used to compare the kinetics of protein folding in the presence and absence of N-phenyl-methyl-N,N-dimethylammonium-propane-sulfonate (NDSB 256). Hen lysozyme and the beta2 subunit of Escherichia coli tryptophan synthase were chosen as model systems since their folding pathways had been previously investigated in detail. It is shown that, massive aggregation of tryptophan synthase occurs within less than 2.5 s after dilution in the renaturation buffer, but can be prevented by NDSB 256; only very early folding phases (such as the formation of a loosely packed hydrophobic core able to bind 8-anilino-1-naphthalenesulphonic acid, and the initial burying of tryptophan 177) are significantly altered by NDSB 256; none of the later phases is affected. Furthermore, NDSB 256 did not significantly affect any of the kinetic phases observed during the refolding of denatured lysozyme retaining intact disulphide bonds. This shows that NDSB 256 only interferes with very early steps in the folding process and acts by limiting the abortive interactions that could lead to the formation of inactive aggregates.
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PMID:Interactions of non-detergent sulfobetaines with early folding intermediates facilitate in vitro protein renaturation. 974 55

Some non-detergent sulfobetaines had been shown to prevent aggregation and improve the yield of active proteins when added to the buffer during in vitro protein renaturation. With the aim of designing more efficient folding helpers, a series of non-detergent sulfobetaines have been synthesized and their efficiency in improving the renaturation of a variety of proteins (E. coli tryptophan synthase and beta-D-galactosidase, hen lysozyme, bovine serum albumin, a monoclonal antibody) have been investigated. Attempts to correlate the structure of each sulfobetaines with its effect on folding revealed some molecular features that appear important in helping renaturation. This enabled us to design and synthesize new non-detergent sulfobetaines that act as potent folding helpers.
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PMID:Physical-chemical features of non-detergent sulfobetaines active as protein-folding helpers. 1264 84