2vca: Difference between revisions

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New page: left|200px {{Structure |PDB= 2vca |SIZE=350|CAPTION= <scene name='initialview01'>2vca</scene>, resolution 2.05Å |SITE= <scene name='pdbsite=AC1:Nag+Binding+Site+...
 
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[[Image:2vca.jpg|left|200px]]


{{Structure
==Family 89 glycoside hydrolase from Clostridium perfringens in complex with beta-N-acetyl-D-glucosamine==
|PDB= 2vca |SIZE=350|CAPTION= <scene name='initialview01'>2vca</scene>, resolution 2.05&Aring;
<StructureSection load='2vca' size='340' side='right'caption='[[2vca]], [[Resolution|resolution]] 2.05&Aring;' scene=''>
|SITE= <scene name='pdbsite=AC1:Nag+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Gol+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:Gol+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC4:Gol+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:So4+Binding+Site+For+Chain+A'>AC5</scene> and <scene name='pdbsite=AC6:Ca+Binding+Site+For+Chain+A'>AC6</scene>
== Structural highlights ==
|LIGAND= <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
<table><tr><td colspan='2'>[[2vca]] is a 1 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=2VCA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VCA FirstGlance]. <br>
|ACTIVITY= [http://en.wikipedia.org/wiki/Alpha-N-acetylglucosaminidase Alpha-N-acetylglucosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.50 3.2.1.50]  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.05&#8491;</td></tr>
|GENE=  
<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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2vca FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vca OCA], [https://pdbe.org/2vca PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vca RCSB], [https://www.ebi.ac.uk/pdbsum/2vca PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vca ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A0H2YU91_CLOP1 A0A0H2YU91_CLOP1]
== 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/vc/2vca_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=2vca ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mucopolysaccharidosis III (MPS III) has four forms (A-D) that result from buildup of an improperly degraded glycosaminoglycan in lysosomes. MPS IIIB is attributable to the decreased activity of a lysosomal alpha-N-acetylglucosaminidase (NAGLU). Here, we describe the structure, catalytic mechanism, and inhibition of CpGH89 from Clostridium perfringens, a close bacterial homolog of NAGLU. The structure enables the generation of a homology model of NAGLU, an enzyme that has resisted structural studies despite having been studied for &gt;20 years. This model reveals which mutations giving rise to MPS IIIB map to the active site and which map to regions distant from the active site. The identification of potent inhibitors of CpGH89 and the structures of these inhibitors in complex with the enzyme suggest small-molecule candidates for use as chemical chaperones. These studies therefore illuminate the genetic basis of MPS IIIB, provide a clear biochemical rationale for the necessary sequential action of heparan-degrading enzymes, and open the door to the design and optimization of chemical chaperones for treating MPS IIIB.


'''FAMILY 89 GLYCOSIDE HYDROLASE FROM CLOSTRIDIUM PERFRINGENS IN COMPLEX WITH BETA-N-ACETYL-D-GLUCOSAMINE'''
Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB.,Ficko-Blean E, Stubbs KA, Nemirovsky O, Vocadlo DJ, Boraston AB Proc Natl Acad Sci U S A. 2008 May 6;105(18):6560-5. Epub 2008 Apr 28. PMID:18443291<ref>PMID:18443291</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
==About this Structure==
</div>
2VCA is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_perfringens Clostridium perfringens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VCA OCA].
<div class="pdbe-citations 2vca" style="background-color:#fffaf0;"></div>
[[Category: Alpha-N-acetylglucosaminidase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Clostridium perfringens]]
[[Category: Clostridium perfringens]]
[[Category: Single protein]]
[[Category: Large Structures]]
[[Category: Berg, O.]]
[[Category: Berg O]]
[[Category: Boraston, A B.]]
[[Category: Boraston AB]]
[[Category: Ficko-Blean, E.]]
[[Category: Ficko-Blean E]]
[[Category: Stubbs, K A.]]
[[Category: Stubbs KA]]
[[Category: Vocadlo, D J.]]
[[Category: Vocadlo DJ]]
[[Category: CA]]
[[Category: GOL]]
[[Category: NAG]]
[[Category: SO4]]
[[Category: alpha-n-acetylglucosaminidase]]
[[Category: beta-n-acetyl-d-glucosamine]]
[[Category: family 89 glycoside hydrolase]]
[[Category: gh89]]
[[Category: hydrolase]]
[[Category: mucopolysaccharidosis]]
[[Category: naglu]]
[[Category: sanfilippo disease]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:45:24 2008''

Latest revision as of 12:57, 9 May 2024

Family 89 glycoside hydrolase from Clostridium perfringens in complex with beta-N-acetyl-D-glucosamineFamily 89 glycoside hydrolase from Clostridium perfringens in complex with beta-N-acetyl-D-glucosamine

Structural highlights

2vca is a 1 chain structure with sequence from Clostridium perfringens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.05Å
Ligands:, , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

A0A0H2YU91_CLOP1

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

Mucopolysaccharidosis III (MPS III) has four forms (A-D) that result from buildup of an improperly degraded glycosaminoglycan in lysosomes. MPS IIIB is attributable to the decreased activity of a lysosomal alpha-N-acetylglucosaminidase (NAGLU). Here, we describe the structure, catalytic mechanism, and inhibition of CpGH89 from Clostridium perfringens, a close bacterial homolog of NAGLU. The structure enables the generation of a homology model of NAGLU, an enzyme that has resisted structural studies despite having been studied for >20 years. This model reveals which mutations giving rise to MPS IIIB map to the active site and which map to regions distant from the active site. The identification of potent inhibitors of CpGH89 and the structures of these inhibitors in complex with the enzyme suggest small-molecule candidates for use as chemical chaperones. These studies therefore illuminate the genetic basis of MPS IIIB, provide a clear biochemical rationale for the necessary sequential action of heparan-degrading enzymes, and open the door to the design and optimization of chemical chaperones for treating MPS IIIB.

Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB.,Ficko-Blean E, Stubbs KA, Nemirovsky O, Vocadlo DJ, Boraston AB Proc Natl Acad Sci U S A. 2008 May 6;105(18):6560-5. Epub 2008 Apr 28. PMID:18443291[1]

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

References

  1. ↑ Ficko-Blean E, Stubbs KA, Nemirovsky O, Vocadlo DJ, Boraston AB. Structural and mechanistic insight into the basis of mucopolysaccharidosis IIIB. Proc Natl Acad Sci U S A. 2008 May 6;105(18):6560-5. Epub 2008 Apr 28. PMID:18443291

2vca, resolution 2.05Å

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