4a2s: Difference between revisions
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==Structure of the engineered retro-aldolase RA95.5== | |||
<StructureSection load='4a2s' size='340' side='right' caption='[[4a2s]], [[Resolution|resolution]] 1.40Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4a2s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Sulfolobus_solfataricus Sulfolobus solfataricus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A2S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4A2S FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3NK:1-(6-METHOXYNAPHTHALEN-2-YL)BUTANE-1,3-DIONE'>3NK</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4a2r|4a2r]], [[1lbl|1lbl]], [[1jul|1jul]], [[1juk|1juk]], [[1igs|1igs]], [[2c3z|2c3z]], [[1a53|1a53]], [[1lbf|1lbf]]</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Indole-3-glycerol-phosphate_synthase Indole-3-glycerol-phosphate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.1.1.48 4.1.1.48] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4a2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a2s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4a2s RCSB], [http://www.ebi.ac.uk/pdbsum/4a2s PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Evolutionary advances are often fueled by unanticipated innovation. Directed evolution of a computationally designed enzyme suggests that pronounced molecular changes can also drive the optimization of primitive protein active sites. The specific activity of an artificial retro-aldolase was boosted >4,400-fold by random mutagenesis and screening, affording catalytic efficiencies approaching those of natural enzymes. However, structural and mechanistic studies reveal that the engineered catalytic apparatus, consisting of a reactive lysine and an ordered water molecule, was unexpectedly abandoned in favor of a new lysine residue in a substrate-binding pocket created during the optimization process. Structures of the initial in silico design, a mechanistically promiscuous intermediate and one of the most evolved variants highlight the importance of loop mobility and supporting functional groups in the emergence of the new catalytic center. Such internal competition between alternative reactive sites may have characterized the early evolution of many natural enzymes. | |||
Evolution of a designed retro-aldolase leads to complete active site remodeling.,Giger L, Caner S, Obexer R, Kast P, Baker D, Ban N, Hilvert D Nat Chem Biol. 2013 Jun 9. doi: 10.1038/nchembio.1276. PMID:23748672<ref>PMID:23748672</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
==See Also== | |||
*[[Indole-3-glycerol phosphate synthase|Indole-3-glycerol phosphate synthase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Indole-3-glycerol-phosphate synthase]] | [[Category: Indole-3-glycerol-phosphate synthase]] | ||
[[Category: Sulfolobus solfataricus]] | [[Category: Sulfolobus solfataricus]] | ||
[[Category: Baker, D | [[Category: Baker, D]] | ||
[[Category: Ban, N | [[Category: Ban, N]] | ||
[[Category: Caner, S | [[Category: Caner, S]] | ||
[[Category: Giger, L | [[Category: Giger, L]] | ||
[[Category: Hilvert, D | [[Category: Hilvert, D]] | ||
[[Category: Kast, P | [[Category: Kast, P]] | ||
[[Category: Directed evolution]] | [[Category: Directed evolution]] | ||
[[Category: Engineered enzyme]] | [[Category: Engineered enzyme]] | ||
[[Category: Lyase]] | [[Category: Lyase]] | ||
Revision as of 12:27, 21 December 2014
Structure of the engineered retro-aldolase RA95.5Structure of the engineered retro-aldolase RA95.5
Structural highlights
Publication Abstract from PubMedEvolutionary advances are often fueled by unanticipated innovation. Directed evolution of a computationally designed enzyme suggests that pronounced molecular changes can also drive the optimization of primitive protein active sites. The specific activity of an artificial retro-aldolase was boosted >4,400-fold by random mutagenesis and screening, affording catalytic efficiencies approaching those of natural enzymes. However, structural and mechanistic studies reveal that the engineered catalytic apparatus, consisting of a reactive lysine and an ordered water molecule, was unexpectedly abandoned in favor of a new lysine residue in a substrate-binding pocket created during the optimization process. Structures of the initial in silico design, a mechanistically promiscuous intermediate and one of the most evolved variants highlight the importance of loop mobility and supporting functional groups in the emergence of the new catalytic center. Such internal competition between alternative reactive sites may have characterized the early evolution of many natural enzymes. Evolution of a designed retro-aldolase leads to complete active site remodeling.,Giger L, Caner S, Obexer R, Kast P, Baker D, Ban N, Hilvert D Nat Chem Biol. 2013 Jun 9. doi: 10.1038/nchembio.1276. PMID:23748672[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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