5ly7: Difference between revisions
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==Crystal structure of NagZ H174A mutant from Pseudomonas aeruginosa in complex with the inhibitor 2-acetamido-1,2-dideoxynojirimycin== | |||
<StructureSection load='5ly7' size='340' side='right' caption='[[5ly7]], [[Resolution|resolution]] 3.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5ly7]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LY7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LY7 FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NOK:2-ACETAMIDO-1,2-DIDEOXYNOJIRMYCIN'>NOK</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></td></tr> | |||
<tr id='activity'><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 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=5ly7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ly7 OCA], [http://pdbe.org/5ly7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ly7 RCSB], [http://www.ebi.ac.uk/pdbsum/5ly7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ly7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/NAGZ_PSEAE NAGZ_PSEAE]] 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.[HAMAP-Rule:MF_00364] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The N-acetylglucosaminidase NagZ of Pseudomonas aeruginosa catalyzes the first cytoplasmic step in recycling of muropeptides, cell-wall-derived natural products. This reaction regulates gene expression for the beta-lactam resistance enzyme, beta-lactamase. The enzyme catalyzes hydrolysis of N-acetyl-beta-d-glucosamine-(1-->4)-1,6-anhydro-N-acetyl-beta-d-muramyl-peptide (1) to N-acetyl-beta-d-glucosamine (2) and 1,6-anhydro-N-acetyl-beta-d-muramyl-peptide (3). The structural and functional aspects of catalysis by NagZ were investigated by a total of seven X-ray structures, three computational models based on the X-ray structures, molecular-dynamics simulations and mutagenesis. The structural insights came from the unbound state and complexes of NagZ with the substrate, products and a mimetic of the transient oxocarbenium species, which were prepared by synthesis. The mechanism involves a histidine as acid/base catalyst, which is unique for glycosidases. The turnover process utilizes covalent modification of D244, requiring two transition-state species and is regulated by coordination with a zinc ion. The analysis provides a seamless continuum for the catalytic cycle, incorporating large motions by four loops that surround the active site. | |||
Catalytic Cycle of the N-Acetylglucosaminidase NagZ from Pseudomonas aeruginosa.,Acebron I, Mahasenan KV, De Benedetti S, Lee M, Artola-Recolons C, Hesek D, Wang H, Hermoso JA, Mobashery S J Am Chem Soc. 2017 May 10. doi: 10.1021/jacs.7b01626. PMID:28482153<ref>PMID:28482153</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5ly7" style="background-color:#fffaf0;"></div> | |||
== References == | |||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Beta-N-acetylhexosaminidase]] | |||
[[Category: Acebron, I]] | [[Category: Acebron, I]] | ||
[[Category: Artola-Recolons, C]] | [[Category: Artola-Recolons, C]] | ||
[[Category: Hermoso, J A]] | |||
[[Category: Mahasenan, K]] | |||
[[Category: Mobashery, S]] | |||
[[Category: Cell-wall recycling beta-hexosaminidase pseudomonas aeruginosa inhibitor]] | |||
[[Category: Gene regulation]] | |||
Revision as of 18:44, 17 May 2017
Crystal structure of NagZ H174A mutant from Pseudomonas aeruginosa in complex with the inhibitor 2-acetamido-1,2-dideoxynojirimycinCrystal structure of NagZ H174A mutant from Pseudomonas aeruginosa in complex with the inhibitor 2-acetamido-1,2-dideoxynojirimycin
Structural highlights
Function[NAGZ_PSEAE] 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.[HAMAP-Rule:MF_00364] Publication Abstract from PubMedThe N-acetylglucosaminidase NagZ of Pseudomonas aeruginosa catalyzes the first cytoplasmic step in recycling of muropeptides, cell-wall-derived natural products. This reaction regulates gene expression for the beta-lactam resistance enzyme, beta-lactamase. The enzyme catalyzes hydrolysis of N-acetyl-beta-d-glucosamine-(1-->4)-1,6-anhydro-N-acetyl-beta-d-muramyl-peptide (1) to N-acetyl-beta-d-glucosamine (2) and 1,6-anhydro-N-acetyl-beta-d-muramyl-peptide (3). The structural and functional aspects of catalysis by NagZ were investigated by a total of seven X-ray structures, three computational models based on the X-ray structures, molecular-dynamics simulations and mutagenesis. The structural insights came from the unbound state and complexes of NagZ with the substrate, products and a mimetic of the transient oxocarbenium species, which were prepared by synthesis. The mechanism involves a histidine as acid/base catalyst, which is unique for glycosidases. The turnover process utilizes covalent modification of D244, requiring two transition-state species and is regulated by coordination with a zinc ion. The analysis provides a seamless continuum for the catalytic cycle, incorporating large motions by four loops that surround the active site. Catalytic Cycle of the N-Acetylglucosaminidase NagZ from Pseudomonas aeruginosa.,Acebron I, Mahasenan KV, De Benedetti S, Lee M, Artola-Recolons C, Hesek D, Wang H, Hermoso JA, Mobashery S J Am Chem Soc. 2017 May 10. doi: 10.1021/jacs.7b01626. PMID:28482153[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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