8cqf: Difference between revisions

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== Function ==

[https://www.uniprot.org/uniprot/AMY_PSEHA AMY_PSEHA]

== Publication Abstract from PubMed ==

Cold-adapted enzymes are characterized both by a higher catalytic activity at low temperatures and by having their temperature optimum down-shifted, compared to mesophilic orthologs. In several cases, the optimum does not coincide with the onset of protein melting but reflects some other type of inactivation. In the psychrophilic alpha-amylase from an Antarctic bacterium, the inactivation is thought to originate from a specific enzyme-substrate interaction that breaks around room temperature. Here, we report a computational redesign of this enzyme aimed at shifting its temperature optimum upward. A set of mutations designed to stabilize the enzyme-substrate interaction were predicted by computer simulations of the catalytic reaction at different temperatures. The predictions were verified by kinetic experiments and crystal structures of the redesigned alpha-amylase, showing that the temperature optimum is indeed markedly shifted upward and that the critical surface loop controlling the temperature dependence approaches the target conformation observed in a mesophilic ortholog.

Computational design of the temperature optimum of an enzyme reaction.,van der Ent F, Skagseth S, Lund BA, Socan J, Griese JJ, Brandsdal BO, Aqvist J Sci Adv. 2023 Jun 28;9(26):eadi0963. doi: 10.1126/sciadv.adi0963. Epub 2023 Jun , 28. PMID:37379391<ref>PMID:37379391</ref>

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

== References ==

__TOC__

</StructureSection>

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 == Function ==
 [https://www.uniprot.org/uniprot/AMY_PSEHA AMY_PSEHA]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cold-adapted enzymes are characterized both by a higher catalytic activity at low temperatures and by having their temperature optimum down-shifted, compared to mesophilic orthologs. In several cases, the optimum does not coincide with the onset of protein melting but reflects some other type of inactivation. In the psychrophilic alpha-amylase from an Antarctic bacterium, the inactivation is thought to originate from a specific enzyme-substrate interaction that breaks around room temperature. Here, we report a computational redesign of this enzyme aimed at shifting its temperature optimum upward. A set of mutations designed to stabilize the enzyme-substrate interaction were predicted by computer simulations of the catalytic reaction at different temperatures. The predictions were verified by kinetic experiments and crystal structures of the redesigned alpha-amylase, showing that the temperature optimum is indeed markedly shifted upward and that the critical surface loop controlling the temperature dependence approaches the target conformation observed in a mesophilic ortholog.
+Computational design of the temperature optimum of an enzyme reaction.,van der Ent F, Skagseth S, Lund BA, Socan J, Griese JJ, Brandsdal BO, Aqvist J Sci Adv. 2023 Jun 28;9(26):eadi0963. doi: 10.1126/sciadv.adi0963. Epub 2023 Jun , 28. PMID:37379391<ref>PMID:37379391</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 8cqf" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
 __TOC__
 </StructureSection>