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  • Title: Extracellular enzymes: gene regulation and structure function relationship studies.
    Author: Jarnagin AS, Ferrari E.
    Journal: Biotechnology; 1992; 22():189-217. PubMed ID: 1504587.
    Abstract:
    The first conclusion that one could make from the literature covered in this section is that most single mutations in subtilisin BPN'n do not cause major structural alterations. Even multiple mutations, though they may cause local minor perturbations at each of the altered sites, do not affect the overall structure to a large degree. Bott and Ultsch (1986) observed that the subtilisin BPN' structure is very tolerant of single mutations, and this tolerance may have been necessary for survival of the enzyme during the course of evolution. This structural tolerance is not all that surprising if one considers that the structure of subtilisin Carlsberg is very similar to that of subtilisin BPN' while the protein sequences differ by 31%. A superposition of the 274 alpha-carbon atoms of the two enzymes gives a root mean square (rms) deviation of 0.053 nm, a value indicating significant structural similarity (McPhalen and James 1988). Furthermore, the fungal enzyme proteinase K, which is classified as part of the subtilisin family, has approximately 38-40% sequence homology with bacilli subtilisins, particularly in the catalytic site and substrate-binding regions (Betzel et al. 1988). For these sequence-homology regions there is also a structural similarity indicated by a least squares superposition of alpha-carbons giving an rms deviation of 0.11 nm (Betzel et al. 1988). Thermitase, also a member of the subtilisin family, has 47% sequence homology to subtilisin BPN' (Gros et al. 1989). If the best 203 alpha-carbon atoms are superposed, then an rms deviation of 0.05 nm is obtained (Gros et al. 1989). Apparently a significant amount of sequence variation still allows for overall structural similarities in the subtilisin family of enzymes. Though the overall structure of subtilisin is not easily perturbed by single or even multiple mutations, it is clear from the evidence reviewed here that single mutations can lead to very significant effects on the catalytic efficiency, substrate preference, and stability of the enzyme. Analyzing the structural alterations in subtilisin mutants will lead to an understanding of the molecular effects of the mutations at the atomic level. This understanding enables investigators to model and predict the effects of other substitutions, and allows them to focus their efforts on those mutants that are most likely to have the desired properties.(ABSTRACT TRUNCATED AT 400 WORDS)
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