2vvn: Difference between revisions

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{{Seed}}
[[Image:2vvn.png|left|200px]]


<!--
==BtGH84 in complex with NH-Butylthiazoline==
The line below this paragraph, containing "STRUCTURE_2vvn", creates the "Structure Box" on the page.
<StructureSection load='2vvn' size='340' side='right'caption='[[2vvn]], [[Resolution|resolution]] 1.85&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[2vvn]] is a 2 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=2VVN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VVN FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85&#8491;</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=NH4:AMMONIUM+ION'>NH4</scene>, <scene name='pdbligand=NHT:(3AR,5R,6S,7R,7AR)-2-(ETHYLAMINO)-5-(HYDROXYMETHYL)-5,6,7,7A-TETRAHYDRO-3AH-PYRANO[3,2-D][1,3]THIAZOLE-6,7-DIOL'>NHT</scene></td></tr>
{{STRUCTURE_2vvn|  PDB=2vvn  |  SCENE=  }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vvn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vvn OCA], [https://pdbe.org/2vvn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vvn RCSB], [https://www.ebi.ac.uk/pdbsum/2vvn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vvn 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/vv/2vvn_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=2vvn ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pathological hyperphosphorylation of the microtubule-associated protein tau is characteristic of Alzheimer's disease (AD) and the associated tauopathies. The reciprocal relationship between phosphorylation and O-GlcNAc modification of tau and reductions in O-GlcNAc levels on tau in AD brain offers motivation for the generation of potent and selective inhibitors that can effectively enhance O-GlcNAc in vertebrate brain. We describe the rational design and synthesis of such an inhibitor (thiamet-G, K(i) = 21 nM; 1) of human O-GlcNAcase. Thiamet-G decreased phosphorylation of tau in PC-12 cells at pathologically relevant sites including Thr231 and Ser396. Thiamet-G also efficiently reduced phosphorylation of tau at Thr231, Ser396 and Ser422 in both rat cortex and hippocampus, which reveals the rapid and dynamic relationship between O-GlcNAc and phosphorylation of tau in vivo. We anticipate that thiamet-G will find wide use in probing the functional role of O-GlcNAc in vertebrate brain, and it may also offer a route to blocking pathological hyperphosphorylation of tau in AD.


===BTGH84 IN COMPLEX WITH NH-BUTYLTHIAZOLINE===
A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo.,Yuzwa SA, Macauley MS, Heinonen JE, Shan X, Dennis RJ, He Y, Whitworth GE, Stubbs KA, McEachern EJ, Davies GJ, Vocadlo DJ Nat Chem Biol. 2008 Aug;4(8):483-90. Epub 2008 Jun 29. PMID:18587388<ref>PMID:18587388</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2vvn" style="background-color:#fffaf0;"></div>


<!--
==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_18587388}}, adds the Publication Abstract to the page
*[[Beta-Hexosaminidase|Beta-Hexosaminidase]]
(as it appears on PubMed at http://www.pubmed.gov), where 18587388 is the PubMed ID number.
*[[Beta-Hexosaminidase 3D structures|Beta-Hexosaminidase 3D structures]]
-->
*[[O-GlcNAcase|O-GlcNAcase]]
{{ABSTRACT_PUBMED_18587388}}
== References ==
 
<references/>
==About this Structure==
__TOC__
2VVN is a 2 chains structure of sequences from [http://en.wikipedia.org/wiki/Bacteroides_thetaiotaomicron Bacteroides thetaiotaomicron]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VVN OCA].
</StructureSection>
 
[[Category: Bacteroides thetaiotaomicron VPI-5482]]
==Reference==
[[Category: Large Structures]]
A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo., Yuzwa SA, Macauley MS, Heinonen JE, Shan X, Dennis RJ, He Y, Whitworth GE, Stubbs KA, McEachern EJ, Davies GJ, Vocadlo DJ, Nat Chem Biol. 2008 Aug;4(8):483-90. Epub 2008 Jun 29. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18587388 18587388]
[[Category: Davies GJ]]
[[Category: Bacteroides thetaiotaomicron]]
[[Category: He Y]]
[[Category: Beta-N-acetylhexosaminidase]]
[[Category: Davies, G J.]]
[[Category: He, Y.]]
[[Category: Complex]]
[[Category: Glycosidase]]
[[Category: Glycoside hydrolase]]
[[Category: Hydrolase]]
[[Category: Inhibitor]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Dec 24 11:07:21 2008''

Latest revision as of 18:34, 13 December 2023

BtGH84 in complex with NH-ButylthiazolineBtGH84 in complex with NH-Butylthiazoline

Structural highlights

2vvn is a 2 chain structure with sequence from Bacteroides thetaiotaomicron VPI-5482. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.85Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

OGA_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 PubMed

Pathological hyperphosphorylation of the microtubule-associated protein tau is characteristic of Alzheimer's disease (AD) and the associated tauopathies. The reciprocal relationship between phosphorylation and O-GlcNAc modification of tau and reductions in O-GlcNAc levels on tau in AD brain offers motivation for the generation of potent and selective inhibitors that can effectively enhance O-GlcNAc in vertebrate brain. We describe the rational design and synthesis of such an inhibitor (thiamet-G, K(i) = 21 nM; 1) of human O-GlcNAcase. Thiamet-G decreased phosphorylation of tau in PC-12 cells at pathologically relevant sites including Thr231 and Ser396. Thiamet-G also efficiently reduced phosphorylation of tau at Thr231, Ser396 and Ser422 in both rat cortex and hippocampus, which reveals the rapid and dynamic relationship between O-GlcNAc and phosphorylation of tau in vivo. We anticipate that thiamet-G will find wide use in probing the functional role of O-GlcNAc in vertebrate brain, and it may also offer a route to blocking pathological hyperphosphorylation of tau in AD.

A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo.,Yuzwa SA, Macauley MS, Heinonen JE, Shan X, Dennis RJ, He Y, Whitworth GE, Stubbs KA, McEachern EJ, Davies GJ, Vocadlo DJ Nat Chem Biol. 2008 Aug;4(8):483-90. Epub 2008 Jun 29. PMID:18587388[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Yuzwa SA, Macauley MS, Heinonen JE, Shan X, Dennis RJ, He Y, Whitworth GE, Stubbs KA, McEachern EJ, Davies GJ, Vocadlo DJ. A potent mechanism-inspired O-GlcNAcase inhibitor that blocks phosphorylation of tau in vivo. Nat Chem Biol. 2008 Aug;4(8):483-90. Epub 2008 Jun 29. PMID:18587388 doi:http://dx.doi.org/10.1038/nchembio.96

2vvn, resolution 1.85Å

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