7e0x: Difference between revisions
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==Crystal structure of Arabidopsis thaliana HPPD complexed with 4-hydroxyphenylacetic acid== | |||
<StructureSection load='7e0x' size='340' side='right'caption='[[7e0x]], [[Resolution|resolution]] 1.89Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E0X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E0X 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]] 1.887Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4HP:4-HYDROXYPHENYLACETATE'>4HP</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</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=7e0x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e0x OCA], [https://pdbe.org/7e0x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e0x RCSB], [https://www.ebi.ac.uk/pdbsum/7e0x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e0x ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Increasing demands for efficient and versatile chemical reactions have prompted innovations in enzyme engineering. A major challenge in engineering alpha-ketoglutarate-dependent oxygenases is to develop a rational strategy which can be widely used for directly evolving the desired mutant to generate new products. Herein, we report a strategy for rational redesign of a model enzyme, 4-hydroxyphenylpyruvate dioxygenase (HPPD), based on quantum mechanics/molecular mechanics (QM/MM) calculation and molecular dynamic simulations. This strategy enriched our understanding of the HPPD catalytic reaction pathway and led to the discovery of a series of HPPD mutants producing hydroxyphenylacetate (HPA) as the alternative product other than the native product homogentisate. The predicted HPPD-Fe(IV) horizontal lineO-HPA intermediate was further confirmed by the crystal structure of Arabidopsis thaliana HPPD/S267W complexed with HPA. These findings not only provide a good understanding of the structure-function relationship of HPPD but also demonstrate a generally applicable platform for the development of biocatalysts. | |||
Rational Redesign of Enzyme via the Combination of Quantum Mechanics/Molecular Mechanics, Molecular Dynamics, and Structural Biology Study.,Lin HY, Chen X, Dong J, Yang JF, Xiao H, Ye Y, Li LH, Zhan CG, Yang WC, Yang GF J Am Chem Soc. 2021 Sep 29;143(38):15674-15687. doi: 10.1021/jacs.1c06227. Epub, 2021 Sep 20. PMID:34542283<ref>PMID:34542283</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Lin | <div class="pdbe-citations 7e0x" style="background-color:#fffaf0;"></div> | ||
[[Category: Yang | |||
==See Also== | |||
*[[Dioxygenase 3D structures|Dioxygenase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Lin HY]] | |||
[[Category: Yang GF]] | |||
Latest revision as of 11:41, 17 October 2024
Crystal structure of Arabidopsis thaliana HPPD complexed with 4-hydroxyphenylacetic acidCrystal structure of Arabidopsis thaliana HPPD complexed with 4-hydroxyphenylacetic acid
Structural highlights
Publication Abstract from PubMedIncreasing demands for efficient and versatile chemical reactions have prompted innovations in enzyme engineering. A major challenge in engineering alpha-ketoglutarate-dependent oxygenases is to develop a rational strategy which can be widely used for directly evolving the desired mutant to generate new products. Herein, we report a strategy for rational redesign of a model enzyme, 4-hydroxyphenylpyruvate dioxygenase (HPPD), based on quantum mechanics/molecular mechanics (QM/MM) calculation and molecular dynamic simulations. This strategy enriched our understanding of the HPPD catalytic reaction pathway and led to the discovery of a series of HPPD mutants producing hydroxyphenylacetate (HPA) as the alternative product other than the native product homogentisate. The predicted HPPD-Fe(IV) horizontal lineO-HPA intermediate was further confirmed by the crystal structure of Arabidopsis thaliana HPPD/S267W complexed with HPA. These findings not only provide a good understanding of the structure-function relationship of HPPD but also demonstrate a generally applicable platform for the development of biocatalysts. Rational Redesign of Enzyme via the Combination of Quantum Mechanics/Molecular Mechanics, Molecular Dynamics, and Structural Biology Study.,Lin HY, Chen X, Dong J, Yang JF, Xiao H, Ye Y, Li LH, Zhan CG, Yang WC, Yang GF J Am Chem Soc. 2021 Sep 29;143(38):15674-15687. doi: 10.1021/jacs.1c06227. Epub, 2021 Sep 20. PMID:34542283[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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