4cax: Difference between revisions
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==Crystal structure of Aspergillus fumigatus N-myristoyl transferase in complex with myristoyl CoA and a pyrazole sulphonamide ligand (DDD85646)== | ==Crystal structure of Aspergillus fumigatus N-myristoyl transferase in complex with myristoyl CoA and a pyrazole sulphonamide ligand (DDD85646)== | ||
<StructureSection load='4cax' size='340' side='right' caption='[[4cax]], [[Resolution|resolution]] 1.85Å' scene=''> | <StructureSection load='4cax' size='340' side='right'caption='[[4cax]], [[Resolution|resolution]] 1.85Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4cax]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CAX FirstGlance]. <br> | <table><tr><td colspan='2'>[[4cax]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Aspfm Aspfm]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CAX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CAX FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=646:2,6-DICHLORO-4-(2-PIPERAZIN-1-YLPYRIDIN-4-YL)-N-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)BENZENESULFONAMIDE'>646</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=646:2,6-DICHLORO-4-(2-PIPERAZIN-1-YLPYRIDIN-4-YL)-N-(1,3,5-TRIMETHYL-1H-PYRAZOL-4-YL)BENZENESULFONAMIDE'>646</scene>, <scene name='pdbligand=MYA:TETRADECANOYL-COA'>MYA</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cav|4cav]], [[4caw|4caw]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4cav|4cav]], [[4caw|4caw]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycylpeptide_N-tetradecanoyltransferase Glycylpeptide N-tetradecanoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.97 2.3.1.97] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glycylpeptide_N-tetradecanoyltransferase Glycylpeptide N-tetradecanoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.97 2.3.1.97] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cax OCA], [http://pdbe.org/4cax PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cax RCSB], [http://www.ebi.ac.uk/pdbsum/4cax PDBsum]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4cax FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4cax OCA], [http://pdbe.org/4cax PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4cax RCSB], [http://www.ebi.ac.uk/pdbsum/4cax PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4cax ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Aspfm]] | |||
[[Category: Glycylpeptide N-tetradecanoyltransferase]] | [[Category: Glycylpeptide N-tetradecanoyltransferase]] | ||
[[Category: Large Structures]] | |||
[[Category: Aalten, D M.F Van]] | [[Category: Aalten, D M.F Van]] | ||
[[Category: Blair, D E]] | [[Category: Blair, D E]] | ||
Revision as of 12:28, 20 March 2019
Crystal structure of Aspergillus fumigatus N-myristoyl transferase in complex with myristoyl CoA and a pyrazole sulphonamide ligand (DDD85646)Crystal structure of Aspergillus fumigatus N-myristoyl transferase in complex with myristoyl CoA and a pyrazole sulphonamide ligand (DDD85646)
Structural highlights
Function[NMT_ASPFU] Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins. Publication Abstract from PubMedTreatment 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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