2vxk: Difference between revisions
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< | ==Structural comparison between Aspergillus fumigatus and human GNA1== | ||
<StructureSection load='2vxk' size='340' side='right'caption='[[2vxk]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2vxk]] 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=2VXK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VXK 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]] 1.8Å</td></tr> | |||
-- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=16G:N-ACETYL-D-GLUCOSAMINE-6-PHOSPHATE'>16G</scene>, <scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=2vxk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vxk OCA], [https://pdbe.org/2vxk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vxk RCSB], [https://www.ebi.ac.uk/pdbsum/2vxk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vxk ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q4WCU5_ASPFU Q4WCU5_ASPFU] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vx/2vxk_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vxk ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Aspergillus fumigatus is the causative agent of aspergillosis, a frequently invasive colonization of the lungs of immunocompromised patients. GNA1 (D-glucosamine-6-phosphate N-acetyltransferase) catalyses the acetylation of GlcN-6P (glucosamine-6-phosphate) to GlcNAc-6P (N-acetylglucosamine-6-phosphate), a key intermediate in the UDP-GlcNAc biosynthetic pathway. Gene disruption of gna1 in yeast and Candida albicans has provided genetic validation of the enzyme as a potential target. An understanding of potential active site differences between the human and A. fumigatus enzymes is required to enable further work aimed at identifying selective inhibitors for the fungal enzyme. In the present study, we describe crystal structures of both human and A. fumigatus GNA1, as well as their kinetic characterization. The structures show significant differences in the sugar-binding site with, in particular, several non-conservative substitutions near the phosphate-binding pocket. Mutagenesis targeting these differences revealed drastic effects on steady-state kinetics, suggesting that the differences could be exploitable with small-molecule inhibitors. | |||
Structural and kinetic differences between human and Aspergillus fumigatus D-glucosamine-6-phosphate N-acetyltransferase.,Hurtado-Guerrero R, Raimi OG, Min J, Zeng H, Vallius L, Shepherd S, Ibrahim AF, Wu H, Plotnikov AN, van Aalten DM Biochem J. 2008 Oct 15;415(2):217-23. PMID:18601654<ref>PMID:18601654</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2vxk" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aspergillus fumigatus]] | [[Category: Aspergillus fumigatus]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Hurtado-Guerrero R]] | |||
[[Category: Hurtado-Guerrero | [[Category: Ibrahim AFM]] | ||
[[Category: Ibrahim | [[Category: Min J]] | ||
[[Category: Min | [[Category: Plotnikov AN]] | ||
[[Category: Plotnikov | [[Category: Raimi OG]] | ||
[[Category: Raimi | [[Category: Shepherd S]] | ||
[[Category: | [[Category: Vallius L]] | ||
[[Category: Vallius | [[Category: Wu H]] | ||
[[Category: Zeng H]] | |||
[[Category: Wu | [[Category: Van Aalten DMF]] | ||
[[Category: Zeng | |||
[[Category: | |||
Latest revision as of 13:05, 9 May 2024
Structural comparison between Aspergillus fumigatus and human GNA1Structural comparison between Aspergillus fumigatus and human GNA1
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAspergillus fumigatus is the causative agent of aspergillosis, a frequently invasive colonization of the lungs of immunocompromised patients. GNA1 (D-glucosamine-6-phosphate N-acetyltransferase) catalyses the acetylation of GlcN-6P (glucosamine-6-phosphate) to GlcNAc-6P (N-acetylglucosamine-6-phosphate), a key intermediate in the UDP-GlcNAc biosynthetic pathway. Gene disruption of gna1 in yeast and Candida albicans has provided genetic validation of the enzyme as a potential target. An understanding of potential active site differences between the human and A. fumigatus enzymes is required to enable further work aimed at identifying selective inhibitors for the fungal enzyme. In the present study, we describe crystal structures of both human and A. fumigatus GNA1, as well as their kinetic characterization. The structures show significant differences in the sugar-binding site with, in particular, several non-conservative substitutions near the phosphate-binding pocket. Mutagenesis targeting these differences revealed drastic effects on steady-state kinetics, suggesting that the differences could be exploitable with small-molecule inhibitors. Structural and kinetic differences between human and Aspergillus fumigatus D-glucosamine-6-phosphate N-acetyltransferase.,Hurtado-Guerrero R, Raimi OG, Min J, Zeng H, Vallius L, Shepherd S, Ibrahim AF, Wu H, Plotnikov AN, van Aalten DM Biochem J. 2008 Oct 15;415(2):217-23. PMID:18601654[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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