View source for 4a29


==Structure of the engineered retro-aldolase RA95.0==
<StructureSection load='4a29' size='340' side='right'caption='[[4a29]], [[Resolution|resolution]] 1.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4a29]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4A29 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4A29 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3NK:1-(6-METHOXYNAPHTHALEN-2-YL)BUTANE-1,3-DIONE'>3NK</scene>, <scene name='pdbligand=MLT:D-MALATE'>MLT</scene></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=4a29 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4a29 OCA], [https://pdbe.org/4a29 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4a29 RCSB], [https://www.ebi.ac.uk/pdbsum/4a29 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4a29 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRPC_SACS2 TRPC_SACS2] 
<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 &gt;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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4a29" style="background-color:#fffaf0;"></div>

==See Also==
*[[Aldolase 3D structures|Aldolase 3D structures]]
*[[IGPS 3D structures|IGPS 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Baker D]]
[[Category: Ban N]]
[[Category: Caner S]]
[[Category: Giger L]]
[[Category: Hilvert D]]
[[Category: Kast P]]