2xzk: Difference between revisions
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New page: '''Unreleased structure''' The entry 2xzk is ON HOLD until Paper Publication Authors: Telford, J.C., Yeung, J.H.F., Kiefel, M.J., Watts, A.G., Hader, S., Chan, J., Bennet, A.J., Moore, ... |
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==THE ASPERGILLUS FUMIGATUS SIALIDASE IS A KDNASE: STRUCTURAL AND MECHANISTIC INSIGHTS== | |||
<StructureSection load='2xzk' size='340' side='right'caption='[[2xzk]], [[Resolution|resolution]] 1.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2xzk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_fumigatus_Af293 Aspergillus fumigatus Af293]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XZK 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]] 1.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FKD:3-DEOXY-3-FLUORO-D-ERYTHRO-ALPHA-L-MANNO-NON-2-ULOPYRANOSONIC+ACID'>FKD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K99:(2R,3R,4R,5R,6S)-2,3-DIFLUORO-4,5-DIHYDROXY-6-[(1R,2R)-1,2,3-TRIHYDROXYPROPYL]OXANE-2-CARBOXYLIC+ACID'>K99</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</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=2xzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xzk OCA], [https://pdbe.org/2xzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xzk RCSB], [https://www.ebi.ac.uk/pdbsum/2xzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xzk ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/SIA_ASPFU SIA_ASPFU] Sialidase is able to release sialic acid from a wide variety of natural substrates including bovine salivary mucin, colominic acid, bovine fetuin, a serum glycoprotein containing both alpha-2-6 and alpha-2-3-linkages in a ratio of about 3:2, and glycoproteins and glycolipids from thermally denatured human lung epithelial cells. Does not show any trans-sialidase activity since it is able to remove terminal sialic acid residues but is unable to catalyze their transfer to the acceptor substrate. 2-keto-3-deoxynononic acid (KDN) is the preferred substrate and A.fumigatus can utilize KDN as a sole carbon source.<ref>PMID:20652740</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Aspergillus fumigatus is a filamentous fungus that can cause severe respiratory disease in immunocompromised individuals. A putative sialidase from A. fumigatus was recently cloned and shown to be relatively poor in cleaving N-acetylneuraminic acid (Neu5Ac) in comparison to bacterial sialidases. Here we present the first crystal structure of a fungal sialidase. When the apo structure was compared to bacterial sialidase structures, the active site of the Aspergillus enzyme suggested that Neu5Ac would be a poor substrate due to a smaller pocket that normally accommodates the acetamido group of Neu5Ac in sialidases. A sialic acid with a hydroxyl in place of an acetamido group is 2-keto-3-deoxynononic acid (KDN). We show that KDN is the preferred substrate for the A. fumigatus sialidase and that A. fumigatus can utilise KDN as a sole carbon source. A 1.4Angstrom resolution crystal structure of the enzyme in complex with KDN reveals KDN in the active site in a boat conformation, and nearby a second binding site occupied by KDN in a chair conformation, suggesting that polyKDN may be a natural substrate. The enzyme is not inhibited by the sialidase transition state analogue 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) but is inhibited by the related KDN2en that we show bound to the enzyme in a 1.84Angstrom resolution crystal structure. Using a fluorinated KDN substrate, we present a 1.5Angstrom resolution structure of a covalently bound catalytic intermediate. The A. fumigatus sialidase is therefore a KDNase with a similar catalytic mechanism to Neu5Ac exosialidases, and this study represents the first structure of a KDNase. | |||
The Aspergillus fumigatus sialidase is a KDNase: structural and mechanistic insights.,Telford JC, Yeung JH, Xu G, Kiefel MJ, Watts AG, Hader S, Chan J, Bennet AJ, Moore MM, Taylor GL J Biol Chem. 2011 Jan 19. PMID:21247893<ref>PMID:21247893</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2xzk" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Neuraminidase 3D structures|Neuraminidase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Aspergillus fumigatus Af293]] | |||
[[Category: Large Structures]] | |||
[[Category: Bennet AJ]] | |||
[[Category: Chan J]] | |||
[[Category: Hader S]] | |||
[[Category: Kiefel MJ]] | |||
[[Category: Moore MM]] | |||
[[Category: Taylor GL]] | |||
[[Category: Telford JC]] | |||
[[Category: Watts AG]] | |||
[[Category: Yeung JHF]] | |||
