6sdm: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==NADH-dependent variant of TBADH== | ==NADH-dependent variant of TBADH== | ||
<StructureSection load='6sdm' size='340' side='right'caption='[[6sdm]]' scene=''> | <StructureSection load='6sdm' size='340' side='right'caption='[[6sdm]], [[Resolution|resolution]] 2.85Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SDM OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6sdm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_33075 Atcc 33075]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SDM FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">adh ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=29323 ATCC 33075])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Isopropanol_dehydrogenase_(NADP(+)) Isopropanol dehydrogenase (NADP(+))], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.80 1.1.1.80] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6sdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6sdm OCA], [https://pdbe.org/6sdm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6sdm RCSB], [https://www.ebi.ac.uk/pdbsum/6sdm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6sdm ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/ADH_THEBR ADH_THEBR]] Alcohol dehydrogenase with a preference for medium chain secondary alcohols, such as 2-butanol and isopropanol. Has very low activity with primary alcohols, such as ethanol. Under physiological conditions, the enzyme reduces aldehydes and 2-ketones to produce secondary alcohols. Is also active with acetaldehyde and propionaldehyde. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The non-natural needs of industrial applications often require new or improved enzymes. The structures and properties of enzymes are difficult to predict or design de novo. Instead, semi-rational approaches mimicking evolution entail diversification of parent enzymes followed by evaluation of isolated variants. Artificial selection pressures coupling desired enzyme properties to cell growth could overcome this key bottleneck, but are usually narrow in scope. Here we show diverse enzymes using the ubiquitous cofactors nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) can substitute for defective NAD regeneration, representing a very broadly-applicable artificial selection. Inactivation of Escherichia coli genes required for anaerobic NAD regeneration causes a conditional growth defect. Cells are rescued by foreign enzymes connected to the metabolic network only via NAD or NADP, but only when their substrates are supplied. Using this principle, alcohol dehydrogenase, imine reductase and nitroreductase variants with desired selectivity modifications, and a high-performing isopropanol metabolic pathway, are isolated from libraries of millions of variants in single-round experiments with typical limited information to guide design. | |||
Versatile selective evolutionary pressure using synthetic defect in universal metabolism.,Selles Vidal L, Murray JW, Heap JT Nat Commun. 2021 Nov 25;12(1):6859. doi: 10.1038/s41467-021-27266-9. PMID:34824282<ref>PMID:34824282</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6sdm" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Atcc 33075]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Heap | [[Category: Heap, J T]] | ||
[[Category: Murray | [[Category: Murray, J W]] | ||
[[Category: | [[Category: Vidal, L Selles]] | ||
[[Category: Cofactor]] | |||
[[Category: Oxidoreductase]] | |||
Revision as of 10:09, 16 March 2022
NADH-dependent variant of TBADHNADH-dependent variant of TBADH
Structural highlights
Function[ADH_THEBR] Alcohol dehydrogenase with a preference for medium chain secondary alcohols, such as 2-butanol and isopropanol. Has very low activity with primary alcohols, such as ethanol. Under physiological conditions, the enzyme reduces aldehydes and 2-ketones to produce secondary alcohols. Is also active with acetaldehyde and propionaldehyde. Publication Abstract from PubMedThe non-natural needs of industrial applications often require new or improved enzymes. The structures and properties of enzymes are difficult to predict or design de novo. Instead, semi-rational approaches mimicking evolution entail diversification of parent enzymes followed by evaluation of isolated variants. Artificial selection pressures coupling desired enzyme properties to cell growth could overcome this key bottleneck, but are usually narrow in scope. Here we show diverse enzymes using the ubiquitous cofactors nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) can substitute for defective NAD regeneration, representing a very broadly-applicable artificial selection. Inactivation of Escherichia coli genes required for anaerobic NAD regeneration causes a conditional growth defect. Cells are rescued by foreign enzymes connected to the metabolic network only via NAD or NADP, but only when their substrates are supplied. Using this principle, alcohol dehydrogenase, imine reductase and nitroreductase variants with desired selectivity modifications, and a high-performing isopropanol metabolic pathway, are isolated from libraries of millions of variants in single-round experiments with typical limited information to guide design. Versatile selective evolutionary pressure using synthetic defect in universal metabolism.,Selles Vidal L, Murray JW, Heap JT Nat Commun. 2021 Nov 25;12(1):6859. doi: 10.1038/s41467-021-27266-9. PMID:34824282[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||||