5mrq: Difference between revisions
New page: '''Unreleased structure''' The entry 5mrq is ON HOLD Authors: Schwab, A., Illarionov, B., Frank, A., Kunfermann, A., Seet, M., Bacher, A., Witschel, M., Fischer, M., Groll, M., Diederic... |
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==Arabidopsis thaliana IspD Asp262Ala Mutant== | |||
<StructureSection load='5mrq' size='340' side='right'caption='[[5mrq]], [[Resolution|resolution]] 2.20Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5mrq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MRQ 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]] 2.2Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=TRS:2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>TRS</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=5mrq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mrq OCA], [https://pdbe.org/5mrq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mrq RCSB], [https://www.ebi.ac.uk/pdbsum/5mrq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mrq ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/ISPD_ARATH ISPD_ARATH] Enzyme of the plastid non-mevalonate pathway for isoprenoid biosynthesis that catalyzes the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from CTP and 2-C-methyl-D-erythritol 4-phosphate (MEP). Is essential for chloroplast development and required for pigments and gibberellins biosynthesis.<ref>PMID:10841550</ref> <ref>PMID:12029484</ref> <ref>PMID:18236010</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Enzymes of the nonmevalonate pathway of isoprenoid biosynthesis are attractive targets for the development of herbicides and drugs against infectious diseases. While this pathway is essential for many pathogens and plants, mammals do not depend on it for the synthesis of isoprenoids. IspD, the third enzyme of the nonmevalonate pathway, is unique in that it has an allosteric regulatory site. We elucidated the binding mode of phenylisoxazoles, a new class of allosteric inhibitors. Allosteric inhibition is effected by large conformational changes of a loop region proximal to the active site. We investigated the different roles of residues in this loop by mutation studies and identified repulsive interactions with Asp291 and Asp292 to be responsible for inhibition. Crystallographic data and the response of mutant enzymes to three different classes of allosteric inhibitors provide an in-depth understanding of the allosteric mechanism. The obtained mutant enzymes show selective resistance to allosteric inhibitors and provide conceptually valuable information for future engineering of herbicide-resistant crops. We found that the isoprenoid precursors IPP and DMAPP are natural inhibitors of Arabidopsis thaliana IspD; however, they do not seem to bind to the allosteric site. | |||
Mechanism of Allosteric Inhibition of the Enzyme IspD by Three Different Classes of Ligands.,Schwab A, Illarionov B, Frank A, Kunfermann A, Seet M, Bacher A, Witschel MC, Fischer M, Groll M, Diederich F ACS Chem Biol. 2017 Aug 18;12(8):2132-2138. doi: 10.1021/acschembio.7b00004. Epub, 2017 Jul 7. PMID:28686408<ref>PMID:28686408</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5mrq" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[MEP cytidylyltransferase 3D structures|MEP cytidylyltransferase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Arabidopsis thaliana]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Bacher A]] | |||
[[Category: Diederich F]] | |||
[[Category: Fischer M]] | |||
[[Category: Frank A]] | |||
[[Category: Groll M]] | |||
[[Category: Illarionov B]] | |||
[[Category: Kunfermann A]] | |||
[[Category: Schwab A]] | |||
[[Category: Seet M]] | |||
[[Category: Witschel M]] | |||
Latest revision as of 20:47, 8 November 2023
Arabidopsis thaliana IspD Asp262Ala MutantArabidopsis thaliana IspD Asp262Ala Mutant
Structural highlights
FunctionISPD_ARATH Enzyme of the plastid non-mevalonate pathway for isoprenoid biosynthesis that catalyzes the formation of 4-diphosphocytidyl-2-C-methyl-D-erythritol from CTP and 2-C-methyl-D-erythritol 4-phosphate (MEP). Is essential for chloroplast development and required for pigments and gibberellins biosynthesis.[1] [2] [3] Publication Abstract from PubMedEnzymes of the nonmevalonate pathway of isoprenoid biosynthesis are attractive targets for the development of herbicides and drugs against infectious diseases. While this pathway is essential for many pathogens and plants, mammals do not depend on it for the synthesis of isoprenoids. IspD, the third enzyme of the nonmevalonate pathway, is unique in that it has an allosteric regulatory site. We elucidated the binding mode of phenylisoxazoles, a new class of allosteric inhibitors. Allosteric inhibition is effected by large conformational changes of a loop region proximal to the active site. We investigated the different roles of residues in this loop by mutation studies and identified repulsive interactions with Asp291 and Asp292 to be responsible for inhibition. Crystallographic data and the response of mutant enzymes to three different classes of allosteric inhibitors provide an in-depth understanding of the allosteric mechanism. The obtained mutant enzymes show selective resistance to allosteric inhibitors and provide conceptually valuable information for future engineering of herbicide-resistant crops. We found that the isoprenoid precursors IPP and DMAPP are natural inhibitors of Arabidopsis thaliana IspD; however, they do not seem to bind to the allosteric site. Mechanism of Allosteric Inhibition of the Enzyme IspD by Three Different Classes of Ligands.,Schwab A, Illarionov B, Frank A, Kunfermann A, Seet M, Bacher A, Witschel MC, Fischer M, Groll M, Diederich F ACS Chem Biol. 2017 Aug 18;12(8):2132-2138. doi: 10.1021/acschembio.7b00004. Epub, 2017 Jul 7. PMID:28686408[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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