5hq3
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Stable, high-expression variant of human acetylcholinesterase== | |
| + | <StructureSection load='5hq3' size='340' side='right'caption='[[5hq3]], [[Resolution|resolution]] 2.60Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5hq3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HQ3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HQ3 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]] 2.6Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=VX:O-ETHYLMETHYLPHOSPHONIC+ACID+ESTER+GROUP'>VX</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=5hq3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hq3 OCA], [https://pdbe.org/5hq3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hq3 RCSB], [https://www.ebi.ac.uk/pdbsum/5hq3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hq3 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/ACES_HUMAN ACES_HUMAN] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.<ref>PMID:2714437</ref> <ref>PMID:1748670</ref> <ref>PMID:1517212</ref> <ref>PMID:11985878</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Upon heterologous overexpression, many proteins misfold or aggregate, thus resulting in low functional yields. Human acetylcholinesterase (hAChE), an enzyme mediating synaptic transmission, is a typical case of a human protein that necessitates mammalian systems to obtain functional expression. We developed a computational strategy and designed an AChE variant bearing 51 mutations that improved core packing, surface polarity, and backbone rigidity. This variant expressed at approximately 2,000-fold higher levels in E. coli compared to wild-type hAChE and exhibited 20 degrees C higher thermostability with no change in enzymatic properties or in the active-site configuration as determined by crystallography. To demonstrate broad utility, we similarly designed four other human and bacterial proteins. Testing at most three designs per protein, we obtained enhanced stability and/or higher yields of soluble and active protein in E. coli. Our algorithm requires only a 3D structure and several dozen sequences of naturally occurring homologs, and is available at http://pross.weizmann.ac.il. | ||
| - | + | Automated Structure- and Sequence-Based Design of Proteins for High Bacterial Expression and Stability.,Goldenzweig A, Goldsmith M, Hill SE, Gertman O, Laurino P, Ashani Y, Dym O, Unger T, Albeck S, Prilusky J, Lieberman RL, Aharoni A, Silman I, Sussman JL, Tawfik DS, Fleishman SJ Mol Cell. 2016 Jul 21;63(2):337-346. doi: 10.1016/j.molcel.2016.06.012. Epub 2016, Jul 14. PMID:27425410<ref>PMID:27425410</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[ | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5hq3" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: | + | ==See Also== |
| - | [[Category: | + | *[[Acetylcholinesterase 3D structures|Acetylcholinesterase 3D structures]] |
| - | [[Category: | + | *[[Human Acetylcholinesterase|Human Acetylcholinesterase]] |
| - | [[Category: | + | == References == |
| - | [[Category: | + | <references/> |
| - | [[Category: | + | __TOC__ |
| - | [[Category: | + | </StructureSection> |
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Aharoni A]] |
| - | [[Category: | + | [[Category: Albeck S]] |
| - | [[Category: | + | [[Category: Ashani Y]] |
| - | [[Category: Silman | + | [[Category: Dym O]] |
| - | [[Category: | + | [[Category: Fleishman SJ]] |
| + | [[Category: Gertman O]] | ||
| + | [[Category: Goldenzweig A]] | ||
| + | [[Category: Goldsmith M]] | ||
| + | [[Category: Hill SE]] | ||
| + | [[Category: Laurino P]] | ||
| + | [[Category: Lieberman RL]] | ||
| + | [[Category: Prilusky J]] | ||
| + | [[Category: Silman I]] | ||
| + | [[Category: Sussman JL]] | ||
| + | [[Category: Tawfik DS]] | ||
| + | [[Category: Unger T]] | ||
Current revision
Stable, high-expression variant of human acetylcholinesterase
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Categories: Homo sapiens | Large Structures | Aharoni A | Albeck S | Ashani Y | Dym O | Fleishman SJ | Gertman O | Goldenzweig A | Goldsmith M | Hill SE | Laurino P | Lieberman RL | Prilusky J | Silman I | Sussman JL | Tawfik DS | Unger T
