2007
DOI: 10.1002/prot.21670
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Engineering proteins with tunable thermodynamic and kinetic stabilities

Abstract: It is widely recognized that enhancement of protein stability is an important biotechnological goal. However, some applications at least, could actually benefit from stability being strongly dependent on a suitable environment variable, in such a way that enhanced stability or decreased stability could be realized as required. In therapeutic applications, for instance, a long shelf-life under storage conditions may be convenient, but a sufficiently fast degradation of the protein after it has performed the pla… Show more

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Cited by 41 publications
(38 citation statements)
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“…In recent years, computational procedures to design surface charge distributions toward enhancement of protein stability have been developed and tested (18)(19)(20)(21)(22)(23)(24). Our results in HEWL and BLA suggest that these same methods might be extensible to the engineering of folding barriers.…”
Section: Discussionmentioning
confidence: 99%
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“…In recent years, computational procedures to design surface charge distributions toward enhancement of protein stability have been developed and tested (18)(19)(20)(21)(22)(23)(24). Our results in HEWL and BLA suggest that these same methods might be extensible to the engineering of folding barriers.…”
Section: Discussionmentioning
confidence: 99%
“…However, these factors do not permit the fine modulation of folding barriers that could play a significant role in protein function. Recent work shows that surface electrostatic interac-tions are important for protein stability to the extent that it can be enhanced significantly by engineering the charge distribution of proteins (18)(19)(20)(21)(22)(23)(24). Such a role in protein stabilization, together with the realization that proteins sharing the same structure exhibit very different charge distributions (20,25), makes electrostatic interactions good candidates for the tuning of folding/ unfolding free-energy barriers.…”
mentioning
confidence: 99%
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“…Data from the phytases, antibodies, and thioredoxin suggest that about half the time, mutation of an amino acid to the most common amino acid in the MSA for that position is stabilizing. [18][19][20][21][22] On the other hand, the most common amino acid in an unconserved site presumably has little informational value, and furthermore, unconserved sites may still be correlated to each other, which is lost in the consensus. For example, the consensus sequence of TPR motifs has a canonical charge of − 7 although individual TPRs have a 0 ± 2.5 net charge, because the charged residues are largely poorly conserved surface residues that exhibit charge neutralization only when correlation is considered.…”
Section: Introductionmentioning
confidence: 97%
“…Consensus mutations are often viewed as reversions to the ancestral amino acid residues [10] and, consequently, protein stability enhancement could be reasonably attributed to the fact that consensus-sequence proteins may capture to some extent the extreme properties (such as thermophilicity) of ancestral proteins [11][12][13]. The consensus approach has been successfully applied to improve the thermodynamic and thermal stability of several proteins [14][15][16][17][18][19][20]. Interestingly, some of these studies have also shown that the consensus-based approach also improves protein kinetic stability [16][17][18].…”
Section: Introductionmentioning
confidence: 99%