View source for 4caw


==Crystal structure of Aspergillus fumigatus N-myristoyl transferase in complex with myristoyl CoA and a pyrazole sulphonamide ligand==
<StructureSection load='4caw' size='340' side='right'caption='[[4caw]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4caw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus Aspergillus fumigatus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CAW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CAW 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene>, <scene name='pdbligand=P3U:2,6-DICHLORO-4-(2-PIPERAZIN-1-YLPYRIDIN-4-YL)-N-(1,5-DIMETHYL,3-ISOBUTYL-1H-PYRAZOL-4-YL)BENZENESULFONAMIDE'>P3U</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=4caw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4caw OCA], [https://pdbe.org/4caw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4caw RCSB], [https://www.ebi.ac.uk/pdbsum/4caw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4caw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NMT_ASPFU NMT_ASPFU] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Treatment of filamentous fungal infections relies on a limited repertoire of antifungal agents. Compounds possessing novel modes of action are urgently required. N-myristoylation is a ubiquitous modification of eukaryotic proteins. The enzyme N-myristoyltransferase (NMT) has been considered a potential therapeutic target in protozoa and yeasts. Here, we show that the filamentous fungal pathogen Aspergillus fumigatus possesses an active NMT enzyme that is essential for survival. Surprisingly, partial repression of the gene revealed downstream effects of N-myristoylation on cell wall morphology. Screening a library of inhibitors led to the discovery of a pyrazole sulphonamide compound that inhibits the enzyme and is fungicidal under partially repressive nmt conditions. Together with a crystallographic complex showing the inhibitor binding in the peptide substrate pocket, we provide evidence of NMT being a potential drug target in A. fumigatus.

N-myristoyltransferase is a cell wall target in Aspergillus fumigatus.,Fang W, Robinson DA, Raimi OG, Blair DE, Harrison JR, Lockhart DE, Torrie LS, Ruda GF, Wyatt PG, Gilbert IH, van Aalten DM ACS Chem Biol. 2015 Jun 19;10(6):1425-34. doi: 10.1021/cb5008647. Epub 2015 Feb, 27. PMID:25706802<ref>PMID:25706802</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4caw" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aspergillus fumigatus]]
[[Category: Large Structures]]
[[Category: Blair DE]]
[[Category: Fang W]]
[[Category: Gilbert IH]]
[[Category: Harrison J]]
[[Category: Lockhart DEA]]
[[Category: Raimi OG]]
[[Category: Robinson DA]]
[[Category: Ruda GF]]
[[Category: Torrie LS]]
[[Category: Van Aalten DMF]]
[[Category: Wyatt PG]]