2j62: Difference between revisions
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New page: left|200px<br /> <applet load="2j62" size="450" color="white" frame="true" align="right" spinBox="true" caption="2j62, resolution 2.26Å" /> '''STRUCTURE OF A BACT... |
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== | ==Structure of a bacterial O-glcnacase in complex with glcnacstatin== | ||
<StructureSection load='2j62' size='340' side='right'caption='[[2j62]], [[Resolution|resolution]] 2.26Å' scene=''> | |||
[[ | == Structural highlights == | ||
[[ | <table><tr><td colspan='2'>[[2j62]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J62 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2J62 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]] 2.26Å</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=GSZ:N-[(5R,6R,7R,8S)-6,7-DIHYDROXY-5-(HYDROXYMETHYL)-2-(2-PHENYLETHYL)-1,5,6,7,8,8A-HEXAHYDROIMIDAZO[1,2-A]PYRIDIN-8-YL]-2-METHYLPROPANAMIDE'>GSZ</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=2j62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j62 OCA], [https://pdbe.org/2j62 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2j62 RCSB], [https://www.ebi.ac.uk/pdbsum/2j62 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2j62 ProSAT]</span></td></tr> | ||
</table> | |||
[ | == Function == | ||
[[ | [https://www.uniprot.org/uniprot/OGA_CLOP1 OGA_CLOP1] Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. | ||
[ | == 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/j6/2j62_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=2j62 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Many phosphorylation signal transduction pathways in the eukaryotic cell are modulated by posttranslational modification of specific serines/threonines with N-acetylglucosamine (O-GlcNAc). Levels of O-GlcNAc on key proteins regulate biological processes as diverse as the cell cycle, insulin signaling, and protein degradation. The two enzymes involved in this dynamic and abundant modification are the O-GlcNAc transferase and O-GlcNAcase. Structural data have recently revealed that the O-GlcNAcase possesses an active site with significant structural similarity to that of the human lysosomal hexosaminidases HexA/HexB. PUGNAc, an O-GlcNAcase inhibitor widely used to raise levels of O-GlcNAc in human cell lines, also inhibits these hexosaminidases. Here, we have exploited recent structural information of an O-GlcNAcase-PUGNAc complex to design and synthesize a glucoimidazole-based inhibitor, GlcNAcstatin, which is a 5 pM competitive inhibitor of enzymes of the O-GlcNAcase family, shows 100000-fold selectivity over HexA/B, and binds to the O-GlcNAcase active site by mimicking the transition state as revealed by X-ray crystallography. This compound is able to raise O-GlcNAc levels in human HEK 293 and SH-SY5Y neuroblastoma cell lines and thus provides a novel, potent tool for the study of the role of O-GlcNAc in intracellular signal transduction pathways. | |||
GlcNAcstatin: a picomolar, selective O-GlcNAcase inhibitor that modulates intracellular O-glcNAcylation levels.,Dorfmueller HC, Borodkin VS, Schimpl M, Shepherd SM, Shpiro NA, van Aalten DM J Am Chem Soc. 2006 Dec 27;128(51):16484-5. PMID:17177381<ref>PMID:17177381</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2j62" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Hyaluronidase 3D structures|Hyaluronidase 3D structures]] | |||
*[[O-GlcNAcase|O-GlcNAcase]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Clostridium perfringens]] | |||
[[Category: Large Structures]] | |||
[[Category: Borodkin VS]] | |||
[[Category: Dorfmueller HC]] | |||
[[Category: Schimpl M]] | |||
[[Category: Shepherd SM]] | |||
[[Category: Shpiro NA]] | |||
[[Category: Van Aalten DMF]] | |||
Latest revision as of 09:34, 9 May 2024
Structure of a bacterial O-glcnacase in complex with glcnacstatin
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