View source for 7egv


==Acetolactate Synthase from Trichoderma harzianum with inhibitor harzianic acid==
<StructureSection load='7egv' size='340' side='right'caption='[[7egv]], [[Resolution|resolution]] 2.54&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7egv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trichoderma_harzianum Trichoderma harzianum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7EGV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7EGV 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]] 2.54&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=J3L:(2S)-3-methyl-2-[[(2S,4R)-1-methyl-4-[(2E,4E)-octa-2,4-dienoyl]-3,5-bis(oxidanylidene)pyrrolidin-2-yl]methyl]-2-oxidanyl-butanoic+acid'>J3L</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=TZD:2-{3-[(4-AMINO-2-METHYLPYRIMIDIN-5-YL)METHYL]-4-METHYL-2-OXO-2,3-DIHYDRO-1,3-THIAZOL-5-YL}ETHYL+TRIHYDROGEN+DIPHOSPHATE'>TZD</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=7egv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7egv OCA], [https://pdbe.org/7egv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7egv RCSB], [https://www.ebi.ac.uk/pdbsum/7egv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7egv ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A2N1LPC4_TRIHA A0A2N1LPC4_TRIHA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Acetohydroxyacid synthase (AHAS) is the first enzyme in the branched-chain amino acid biosynthetic pathway and is a validated target for herbicide and fungicide development. Here we report harzianic acid (HA, 1) produced by the biocontrol fungus Trichoderma afroharzianum t-22 (Tht22) as a natural product inhibitor of AHAS. The biosynthetic pathway of HA was elucidated with heterologous reconstitution. Guided by a putative self-resistance enzyme in the genome, HA was biochemically demonstrated to be a selective inhibitor of fungal AHAS, including those from phytopathogenic fungi. In addition, HA can inhibit a common resistant variant of AHAS in which the active site proline is mutated. Structural analysis of AHAS complexed with HA revealed the molecular basis of competitive inhibition, which differs from all known commercial AHAS inhibitors. The alternative binding mode also rationalizes the selectivity of HA, as well as effectiveness toward resistant mutants. A proposed role of HA biosynthesis by Tht22 in the rhizosphere is discussed based on the data.

Harzianic Acid from Trichoderma afroharzianum Is a Natural Product Inhibitor of Acetohydroxyacid Synthase.,Xie L, Zang X, Cheng W, Zhang Z, Zhou J, Chen M, Tang Y J Am Chem Soc. 2021 Jun 16. doi: 10.1021/jacs.1c03988. PMID:34132537<ref>PMID:34132537</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7egv" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Trichoderma harzianum]]
[[Category: Chen M]]
[[Category: Tang Y]]
[[Category: Xie L]]
[[Category: Zang X]]
[[Category: Zhou J]]