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| | <StructureSection load='3nz1' size='340' side='right'caption='[[3nz1]], [[Resolution|resolution]] 1.56Å' scene=''> | | <StructureSection load='3nz1' size='340' side='right'caption='[[3nz1]], [[Resolution|resolution]] 1.56Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3nz1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_35091 Atcc 35091]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NZ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NZ1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3nz1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_solfataricus Saccharolobus solfataricus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NZ1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NZ1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3NY:5-NITRO-1H-BENZOTRIAZOLE'>3NY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.56Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3nyz|3nyz]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3NY:5-NITRO-1H-BENZOTRIAZOLE'>3NY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TLA:L(+)-TARTARIC+ACID'>TLA</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">INDOLE-3-GLYCEROLPHOSPHATE SYNTHASE, SSO0895, trpC ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2287 ATCC 35091])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Indole-3-glycerol-phosphate_synthase Indole-3-glycerol-phosphate synthase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3nz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nz1 OCA], [https://pdbe.org/3nz1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nz1 RCSB], [https://www.ebi.ac.uk/pdbsum/3nz1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nz1 ProSAT]</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=3nz1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nz1 OCA], [https://pdbe.org/3nz1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nz1 RCSB], [https://www.ebi.ac.uk/pdbsum/3nz1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nz1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/TRPC_SACS2 TRPC_SACS2] |
| - | A general approach for the computational design of enzymes to catalyze arbitrary reactions is a goal at the forefront of the field of protein design. Recently, computationally designed enzymes have been produced for three chemical reactions through the synthesis and screening of a large number of variants. Here, we present an iterative approach that has led to the development of the most catalytically efficient computationally designed enzyme for the Kemp elimination to date. Previously established computational techniques were used to generate an initial design, HG-1, which was catalytically inactive. Analysis of HG-1 with molecular dynamics simulations (MD) and X-ray crystallography indicated that the inactivity might be due to bound waters and high flexibility of residues within the active site. This analysis guided changes to our design procedure, moved the design deeper into the interior of the protein, and resulted in an active Kemp eliminase, HG-2. The cocrystal structure of this enzyme with a transition state analog (TSA) revealed that the TSA was bound in the active site, interacted with the intended catalytic base in a catalytically relevant manner, but was flipped relative to the design model. MD analysis of HG-2 led to an additional point mutation, HG-3, that produced a further threefold improvement in activity. This iterative approach to computational enzyme design, including detailed MD and structural analysis of both active and inactive designs, promises a more complete understanding of the underlying principles of enzymatic catalysis and furthers progress toward reliably producing active enzymes.
| + | |
| - | | + | |
| - | Iterative approach to computational enzyme design.,Privett HK, Kiss G, Lee TM, Blomberg R, Chica RA, Thomas LM, Hilvert D, Houk KN, Mayo SL Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3790-5. Epub 2012 Feb 22. PMID:22357762<ref>PMID:22357762</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 3nz1" style="background-color:#fffaf0;"></div>
| + | |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Indole-3-glycerol phosphate synthase|Indole-3-glycerol phosphate synthase]] | + | *[[IGPS 3D structures|IGPS 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
| + | |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 35091]] | |
| - | [[Category: Indole-3-glycerol-phosphate synthase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kaiser, J T]] | + | [[Category: Saccharolobus solfataricus]] |
| - | [[Category: Lee, T M]] | + | [[Category: Kaiser JT]] |
| - | [[Category: Mayo, S L]] | + | [[Category: Lee TM]] |
| - | [[Category: Privett, H K]] | + | [[Category: Mayo SL]] |
| - | [[Category: Kemp elimination enzyme]] | + | [[Category: Privett HK]] |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Tim barrel]]
| + | |
