View source for 5mrm


==Arabidopsis thaliana IspD in complex with Isoxazole (4)==
<StructureSection load='5mrm' size='340' side='right'caption='[[5mrm]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mrm]] 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=5MRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MRM 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]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=Q9T:2,4-bis(bromanyl)-6-[3-(trifluoromethyl)-1,2-oxazol-5-yl]phenol'>Q9T</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=5mrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mrm OCA], [https://pdbe.org/5mrm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mrm RCSB], [https://www.ebi.ac.uk/pdbsum/5mrm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mrm 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> 
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5mrm" style="background-color:#fffaf0;"></div>

==See Also==
*[[MEP cytidylyltransferase 3D structures|MEP cytidylyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Arabidopsis thaliana]]
[[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]]