2oxn

From Proteopedia

(Difference between revisions)

Revision as of 14:57, 25 December 2014

Vibrio cholerae family 3 glycoside hydrolase (NagZ) in complex with PUGNAc

Structural highlights

2oxn is a 1 chain structure with sequence from "bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	1tr9, 1y65
Gene:	nagZ ("Bacillo virgola del Koch" Trevisan 1884)
Activity:	Beta-N-acetylhexosaminidase, with EC number 3.2.1.52
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[NAGZ_VIBCH] Plays a role in peptidoglycan recycling by cleaving the terminal beta-1,4-linked N-acetylglucosamine (GlcNAc) from peptide-linked peptidoglycan fragments, giving rise to free GlcNAc, anhydro-N-acetylmuramic acid and anhydro-N-acetylmuramic acid-linked peptides. Plays a role in beta-lactam antibiotic resistance via its role in generating anhydro-N-acetylmuramic acid-linked peptides; these peptides function as signaling molecules that induce high-level expression of the beta-lactamase AmpC.^[1] ^[2] ^[3]

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

The increasing spread of plasmid-borne ampC-ampR operons is of considerable medical importance, since the AmpC beta-lactamases they encode confer high level resistance to many third generation cephalosporins. Induction of AmpC beta-lactamase from endogenous or plasmid-borne ampC-ampR operons is mediated by a catabolic inducer molecule, 1,6-anhydro-N-acetylmuramic acid (MurNAc) tripeptide, an intermediate of the cell wall recycling pathway derived from the peptidoglycan. Here we describe a strategy for attenuating the antibiotic resistance associated with the ampC-ampR operon by blocking the formation of the inducer molecule using small molecule inhibitors of NagZ, the glycoside hydrolase catalyzing the formation of this inducer molecule. The structure of the NagZ-inhibitor complex provides insight into the molecular basis for inhibition and enables the development of inhibitors with 100-fold selectivity for NagZ over functionally related human enzymes. These PUGNAc-derived inhibitors reduce the minimal inhibitory concentration (MIC) values for several clinically relevant cephalosporins in both wild-type and AmpC-hyperproducing strains lacking functional AmpD.

Small molecule inhibitors of a glycoside hydrolase attenuate inducible AmpC-mediated beta-lactam resistance.,Stubbs KA, Balcewich M, Mark BL, Vocadlo DJ J Biol Chem. 2007 Jul 20;282(29):21382-91. Epub 2007 Apr 16. PMID:17439950^[4]

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

References

↑ Stubbs KA, Bacik JP, Perley-Robertson GE, Whitworth GE, Gloster TM, Vocadlo DJ, Mark BL. The Development of Selective Inhibitors of NagZ: Increased Susceptibility of Gram-Negative Bacteria to beta-Lactams. Chembiochem. 2013 Oct 11;14(15):1973-81. doi: 10.1002/cbic.201300395. Epub 2013, Sep 5. PMID:24009110 doi:http://dx.doi.org/10.1002/cbic.201300395
↑ Stubbs KA, Balcewich M, Mark BL, Vocadlo DJ. Small molecule inhibitors of a glycoside hydrolase attenuate inducible AmpC-mediated beta-lactam resistance. J Biol Chem. 2007 Jul 20;282(29):21382-91. Epub 2007 Apr 16. PMID:17439950 doi:10.1074/jbc.M700084200
↑ Balcewich MD, Stubbs KA, He Y, James TW, Davies GJ, Vocadlo DJ, Mark BL. Insight into a strategy for attenuating AmpC-mediated beta-lactam resistance: Structural basis for selective inhibition of the glycoside hydrolase NagZ. Protein Sci. 2009 Apr 16. PMID:19499593 doi:10.1002/pro.137
↑ Stubbs KA, Balcewich M, Mark BL, Vocadlo DJ. Small molecule inhibitors of a glycoside hydrolase attenuate inducible AmpC-mediated beta-lactam resistance. J Biol Chem. 2007 Jul 20;282(29):21382-91. Epub 2007 Apr 16. PMID:17439950 doi:10.1074/jbc.M700084200

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2oxn"

@@ Line 9: / Line 9: @@
 <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2oxn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2oxn OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2oxn RCSB], [http://www.ebi.ac.uk/pdbsum/2oxn PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/NAGZ_VIBCH NAGZ_VIBCH]] Plays a role in peptidoglycan recycling by cleaving the terminal beta-1,4-linked N-acetylglucosamine (GlcNAc) from peptide-linked peptidoglycan fragments, giving rise to free GlcNAc, anhydro-N-acetylmuramic acid and anhydro-N-acetylmuramic acid-linked peptides. Plays a role in beta-lactam antibiotic resistance via its role in generating anhydro-N-acetylmuramic acid-linked peptides; these peptides function as signaling molecules that induce high-level expression of the beta-lactamase AmpC.<ref>PMID:24009110</ref> <ref>PMID:17439950</ref> <ref>PMID:19499593</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 37: / Line 39: @@
 [[Category: Bacillo virgola del koch trevisan 1884]]
 [[Category: Beta-N-acetylhexosaminidase]]
-[[Category: Balcewich, M.]]
+[[Category: Balcewich, M]]
-[[Category: Mark, B L.]]
+[[Category: Mark, B L]]
 [[Category: Hydrolase]]
 [[Category: Tim-barrel]]

2oxn

From Proteopedia

Revision as of 14:57, 25 December 2014

Vibrio cholerae family 3 glycoside hydrolase (NagZ) in complex with PUGNAc

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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