A functional comparison of the TET aminopeptidases of P. furiosus and B. subtilis with a protein-engineered variant recombining the former's structure with the latter's active site
DIR@IMTECH: CSIR-Institute of Microbial Technology
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Title |
A functional comparison of the TET aminopeptidases of P. furiosus and B. subtilis with a protein-engineered variant recombining the former's structure with the latter's active site
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Creator |
Kapoor, Divya
Singh, Balvinder Karthikeyan, Subramanian Guptasarma, Purnananda |
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Subject |
QR Microbiology
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Description |
We have produced and characterized three microbial tetrahedral (TET) aminopeptidases: the previously uncharacterized Bacillus subtilis aminopeptidase (BsuAP), a Pyrococcus furiosus aminopeptidase (PfuAP), and a protein-engineered PfuAP-derived ‘designer’ aminopeptidase (MutAP) in which the entire active site of PfuAP is replaced with that of BsuAP through the making of 9 non-contiguous structure-guided mutations. The temperature/pH values of optimal function of MutAP (60 °C/pH 7.0) were found to be comparable to those of its progenitors, BsuAP (70 °C/pH 7.5) and PfuAP (80 °C/pH 8.0). The Km of MutAP (3.8 mM) was similar to that of PfuAP (5.0 mM) and unlike that of BsuAP (20.8 mM); however, unlike PfuAP, MutAP showed severe substrate-based inhibition like BsuAP, at substrate exceeding 5 mM concentration. MutAP thus inherits certain characteristics from each of its progenitors. At the same time, the Kcat of MutAP was ∼185-fold lower than that of PfuAP and ∼300-fold lower than that of BsuAP, indicating an unanticipated slowing down of activity. The results provide tentative evidence that ‘structure-guided transplantation’ of active sites between proteins can help in recombining enzyme characteristics in interesting and unanticipated ways, to help create novel enzymes.
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Publisher |
Elsevier Science
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Date |
2010
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://crdd.osdd.net/open/1120/1/guptasarma2010.1.pdf
Kapoor, Divya and Singh, Balvinder and Karthikeyan, Subramanian and Guptasarma, Purnananda (2010) A functional comparison of the TET aminopeptidases of P. furiosus and B. subtilis with a protein-engineered variant recombining the former's structure with the latter's active site. Enzyme and Microbial Technology, 46 (1). pp. 1-8. ISSN 01410229 |
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Relation |
http://dx.doi.org/10.1016/j.enzmictec.2009.09.003
http://crdd.osdd.net/open/1120/ |
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