4lis: Difference between revisions
New page: '''Unreleased structure''' The entry 4lis is ON HOLD Authors: Dalrymple, S.A., Ko, J., Sheoran, I., Kaminskyj, S.G.W., Sanders, D.A.R. Description: Crystal Structure of UDP-galactose-4... |
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The | ==Crystal Structure of UDP-galactose-4-epimerase from Aspergillus nidulans== | ||
<StructureSection load='4lis' size='340' side='right'caption='[[4lis]], [[Resolution|resolution]] 2.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4lis]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_nidulans_FGSC_A4 Aspergillus nidulans FGSC A4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LIS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LIS 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]] 2.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene>, <scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</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=4lis FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lis OCA], [https://pdbe.org/4lis PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lis RCSB], [https://www.ebi.ac.uk/pdbsum/4lis PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lis ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/C8VAU8_EMENI C8VAU8_EMENI] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The frequency of invasive fungal infections has rapidly increased in recent years. Current clinical treatments are experiencing decreased potency due to severe host toxicity and the emergence of fungal drug resistance. As such, new targets and their corresponding synthetic pathways need to be explored for drug development purposes. In this context, galactofuranose residues, which are employed in fungal cell wall construction, but are notably absent in animals, represent an appealing target. Herein we present the structural and biochemical characterization of UDP-galactose-4-epimerase from Aspergillus nidulans which produces the precursor UDP-galactopyranose required for galactofuranose synthesis. Examination of the structural model revealed both NAD(+) and UDP-glucopyranose were bound within the active site cleft in a near identical fashion to that found in the Human epimerase. Mutational studies on the conserved catalytic motif support a similar mechanism to that established for the Human counterpart is likely operational within the A. nidulans epimerase. While the K m and k cat for the enzyme were determined to be 0.11 mM and 12.8 s(-1), respectively, a single point mutation, namely L320C, activated the enzyme towards larger N-acetylated substrates. Docking studies designed to probe active site affinity corroborate the experimentally determined activity profiles and support the kinetic inhibition results. | |||
Elucidation of Substrate Specificity in Aspergillus nidulans UDP-Galactose-4-Epimerase.,Dalrymple SA, Ko J, Sheoran I, Kaminskyj SG, Sanders DA PLoS One. 2013 Oct 7;8(10):e76803. doi: 10.1371/journal.pone.0076803. PMID:24116166<ref>PMID:24116166</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4lis" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[UDP-galactose 4-epimerase|UDP-galactose 4-epimerase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aspergillus nidulans FGSC A4]] | |||
[[Category: Large Structures]] | |||
[[Category: Dalrymple SA]] | |||
[[Category: Kaminskyj SGW]] | |||
[[Category: Ko J]] | |||
[[Category: Sanders DAR]] | |||
[[Category: Sheoran I]] | |||
Latest revision as of 19:19, 20 September 2023
Crystal Structure of UDP-galactose-4-epimerase from Aspergillus nidulansCrystal Structure of UDP-galactose-4-epimerase from Aspergillus nidulans
Structural highlights
FunctionPublication Abstract from PubMedThe frequency of invasive fungal infections has rapidly increased in recent years. Current clinical treatments are experiencing decreased potency due to severe host toxicity and the emergence of fungal drug resistance. As such, new targets and their corresponding synthetic pathways need to be explored for drug development purposes. In this context, galactofuranose residues, which are employed in fungal cell wall construction, but are notably absent in animals, represent an appealing target. Herein we present the structural and biochemical characterization of UDP-galactose-4-epimerase from Aspergillus nidulans which produces the precursor UDP-galactopyranose required for galactofuranose synthesis. Examination of the structural model revealed both NAD(+) and UDP-glucopyranose were bound within the active site cleft in a near identical fashion to that found in the Human epimerase. Mutational studies on the conserved catalytic motif support a similar mechanism to that established for the Human counterpart is likely operational within the A. nidulans epimerase. While the K m and k cat for the enzyme were determined to be 0.11 mM and 12.8 s(-1), respectively, a single point mutation, namely L320C, activated the enzyme towards larger N-acetylated substrates. Docking studies designed to probe active site affinity corroborate the experimentally determined activity profiles and support the kinetic inhibition results. Elucidation of Substrate Specificity in Aspergillus nidulans UDP-Galactose-4-Epimerase.,Dalrymple SA, Ko J, Sheoran I, Kaminskyj SG, Sanders DA PLoS One. 2013 Oct 7;8(10):e76803. doi: 10.1371/journal.pone.0076803. PMID:24116166[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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