3gs6

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:3gs6.png|left|200px]]
+
==Vibrio Cholerea family 3 glycoside hydrolase (NagZ)in complex with N-butyryl-PUGNAc==
 +
<StructureSection load='3gs6' size='340' side='right' caption='[[3gs6]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[3gs6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GS6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GS6 FirstGlance]. <br>
 +
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NP6:[[(3R,4R,5S,6R)-3-(BUTANOYLAMINO)-4,5-DIHYDROXY-6-(HYDROXYMETHYL)OXAN-2-YLIDENE]AMINO]+N-PHENYLCARBAMATE'>NP6</scene><br>
 +
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2oxn|2oxn]], [[1tr9|1tr9]], [[1y65|1y65]], [[3gsm|3gsm]]</td></tr>
 +
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">nagZ, VC_0692 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=666 Vibrio cholerae])</td></tr>
 +
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-N-acetylhexosaminidase Beta-N-acetylhexosaminidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.52 3.2.1.52] </span></td></tr>
 +
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3gs6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gs6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gs6 RCSB], [http://www.ebi.ac.uk/pdbsum/3gs6 PDBsum]</span></td></tr>
 +
<table>
 +
== 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/gs/3gs6_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/chain_selection.php?pdb_ID=2ata ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
NagZ is an exo-N-acetyl-beta-glucosaminidase, found within Gram-negative bacteria, that acts in the peptidoglycan recycling pathway to cleave N-acetylglucosamine residues off peptidoglycan fragments. This activity is required for resistance to cephalosporins mediated by inducible AmpC beta-lactamase. NagZ uses a catalytic mechanism involving a covalent glycosyl enzyme intermediate, unlike that of the human exo-N-acetyl-beta-glucosaminidases: O-GlcNAcase and the beta-hexosaminidase isoenzymes. These latter enzymes, which remove GlcNAc from glycoconjugates, use a neighboring-group catalytic mechanism that proceeds through an oxazoline intermediate. Exploiting these mechanistic differences we previously developed 2-N-acyl derivatives of O-(2-acetamido-2-deoxy-D-glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc), which selectively inhibits NagZ over the functionally related human enzymes and attenuate antibiotic resistance in Gram-negatives that harbor inducible AmpC. To understand the structural basis for the selectivity of these inhibitors for NagZ, we have determined its crystallographic structure in complex with N-valeryl-PUGNAc, the most selective known inhibitor of NagZ over both the human beta-hexosaminidases and O-GlcNAcase. The selectivity stems from the five-carbon acyl chain of N-valeryl-PUGNAc, which we found ordered within the enzyme active site. In contrast, a structure determination of a human O-GlcNAcase homologue bound to a related inhibitor N-butyryl-PUGNAc, which bears a four-carbon chain and is selective for both NagZ and O-GlcNAcase over the human beta-hexosamnidases, reveals that this inhibitor induces several conformational changes in the active site of this O-GlcNAcase homologue. A comparison of these complexes, and with the human beta-hexosaminidases, reveals how selectivity for NagZ can be engineered by altering the 2-N-acyl substituent of PUGNAc to develop inhibitors that repress AmpC mediated beta-lactam resistance.
-
{{STRUCTURE_3gs6| PDB=3gs6 | SCENE= }}
+
Insight into a strategy for attenuating AmpC-mediated beta-lactam resistance: Structural basis for selective inhibition of the glycoside hydrolase NagZ.,Balcewich MD, Stubbs KA, He Y, James TW, Davies GJ, Vocadlo DJ, Mark BL Protein Sci. 2009 Apr 16. PMID:19499593<ref>PMID:19499593</ref>
-
===Vibrio Cholerea family 3 glycoside hydrolase (NagZ)in complex with N-butyryl-PUGNAc===
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
 
+
</div>
-
{{ABSTRACT_PUBMED_19499593}}
+
-
 
+
-
==About this Structure==
+
-
[[3gs6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GS6 OCA].
+
==See Also==
==See Also==
*[[Beta-Hexosaminidase|Beta-Hexosaminidase]]
*[[Beta-Hexosaminidase|Beta-Hexosaminidase]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:019499593</ref><references group="xtra"/>
+
__TOC__
 +
</StructureSection>
[[Category: Beta-N-acetylhexosaminidase]]
[[Category: Beta-N-acetylhexosaminidase]]
[[Category: Vibrio cholerae]]
[[Category: Vibrio cholerae]]

Revision as of 11:02, 29 September 2014

Vibrio Cholerea family 3 glycoside hydrolase (NagZ)in complex with N-butyryl-PUGNAc

3gs6, resolution 2.30Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Views
Personal tools
Navigation
Toolbox