2w4x: Difference between revisions
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< | ==BtGH84 in complex with STZ== | ||
<StructureSection load='2w4x' size='340' side='right'caption='[[2w4x]], [[Resolution|resolution]] 2.42Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2w4x]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron_VPI-5482 Bacteroides thetaiotaomicron VPI-5482]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2W4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2W4X 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]] 2.42Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=STZ:STREPTOZOTOCIN'>STZ</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=2w4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2w4x OCA], [https://pdbe.org/2w4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2w4x RCSB], [https://www.ebi.ac.uk/pdbsum/2w4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2w4x ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/OGA_BACTN OGA_BACTN] 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/w4/2w4x_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=2w4x ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Despite decades of its use in diabetes research, the mechanism of cytotoxicity of streptozotocin (STZ) toward pancreatic beta-islet cells has remained a topic of discussion. Although STZ toxicity is likely a function of its capacity to promote DNA alkylation, it has been proposed that STZ induces pancreatic beta-cell death through O-GlcNAcase inhibition. In this report, we explore the binding mode of STZ to a close homolog of human O-GlcNAcase, BtGH84 from Bacteroides thetaiotaomicron. Our results show that STZ binds in the enzyme active site in its intact form, without the formation of a covalent adduct, consistent with solution studies on BtGH84 and human O-GlcNAcase, as well as with structural work on a homolog from Clostridium perfringens. The active site of the BtGH84 is considerably deformed upon STZ binding and as a result the catalytic machinery is expelled from the binding cavity. | |||
Structural insight into the mechanism of streptozotocin inhibition of O-GlcNAcase.,He Y, Martinez-Fleites C, Bubb A, Gloster TM, Davies GJ Carbohydr Res. 2009 Mar 31;344(5):627-31. Epub 2008 Dec 13. PMID:19217614<ref>PMID:19217614</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2w4x" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-Hexosaminidase|Beta-Hexosaminidase]] | |||
*[[Beta-Hexosaminidase 3D structures|Beta-Hexosaminidase 3D structures]] | |||
*[[O-GlcNAcase|O-GlcNAcase]] | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
</StructureSection> | |||
[[Category: Bacteroides thetaiotaomicron VPI-5482]] | |||
== | [[Category: Large Structures]] | ||
< | [[Category: Bubb A]] | ||
[[Category: Bacteroides thetaiotaomicron]] | [[Category: Davies GJ]] | ||
[[Category: | [[Category: He Y]] | ||
[[Category: Bubb | [[Category: Martinez-Fleites C]] | ||
[[Category: Davies | |||
[[Category: He | |||
[[Category: Martinez-Fleites | |||
Latest revision as of 18:43, 13 December 2023
BtGH84 in complex with STZBtGH84 in complex with STZ
Structural highlights
FunctionOGA_BACTN Biological function unknown. Capable of hydrolyzing the glycosidic link of O-GlcNAcylated proteins. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDespite decades of its use in diabetes research, the mechanism of cytotoxicity of streptozotocin (STZ) toward pancreatic beta-islet cells has remained a topic of discussion. Although STZ toxicity is likely a function of its capacity to promote DNA alkylation, it has been proposed that STZ induces pancreatic beta-cell death through O-GlcNAcase inhibition. In this report, we explore the binding mode of STZ to a close homolog of human O-GlcNAcase, BtGH84 from Bacteroides thetaiotaomicron. Our results show that STZ binds in the enzyme active site in its intact form, without the formation of a covalent adduct, consistent with solution studies on BtGH84 and human O-GlcNAcase, as well as with structural work on a homolog from Clostridium perfringens. The active site of the BtGH84 is considerably deformed upon STZ binding and as a result the catalytic machinery is expelled from the binding cavity. Structural insight into the mechanism of streptozotocin inhibition of O-GlcNAcase.,He Y, Martinez-Fleites C, Bubb A, Gloster TM, Davies GJ Carbohydr Res. 2009 Mar 31;344(5):627-31. Epub 2008 Dec 13. PMID:19217614[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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