View source for 3nzk


==Structure of LpxC from Yersinia enterocolitica Complexed with CHIR090 Inhibitor==
<StructureSection load='3nzk' size='340' side='right'caption='[[3nzk]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3nzk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Yersinia_enterocolitica Yersinia enterocolitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NZK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NZK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C90:N-{(1S,2R)-2-HYDROXY-1-[(HYDROXYAMINO)CARBONYL]PROPYL}-4-{[4-(MORPHOLIN-4-YLMETHYL)PHENYL]ETHYNYL}BENZAMIDE'>C90</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=3nzk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nzk OCA], [https://pdbe.org/3nzk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nzk RCSB], [https://www.ebi.ac.uk/pdbsum/3nzk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nzk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A1JJJ9_YERE8 A1JJJ9_YERE8] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell (By similarity).[SAAS:SAAS011334_004_013136]
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== Publication Abstract from PubMed ==
The first committed step of lipid A biosynthesis is catalyzed by UDP-(3-O-((R)-3-hydroxymyristoyl))-N-acetylglucosamine deacetylase, a metal-dependent deacetylase also known as LpxC. Because lipid A is essential for bacterial viability, the inhibition of LpxC is an appealing therapeutic strategy for the treatment of Gram-negative bacterial infections. Here we report the 1.79 A resolution X-ray crystal structure of LpxC from Yersinia enterocolitica (YeLpxC) complexed with the potent hydroxamate inhibitor CHIR-090. This enzyme is a nearly identical orthologue of LpxC from Yersinia pestis (99.7% sequence identity), the pathogen that causes bubonic plague. Similar to the inhibition of LpxC from Escherichia coli, CHIR-090 inhibits YeLpxC via a two-step slow, tight-binding mechanism with an apparent K(i) of 0.54 +/- 0.14 nM followed by conversion of the E.I to E.I* species with a rate constant of 0.11 +/- 0.01 min(-1). The structure of the LpxC complex with CHIR-090 shows that the inhibitor hydroxamate group chelates the active site zinc ion, and the "tail" of the inhibitor binds in the hydrophobic tunnel in the active site. This hydrophobic tunnel is framed by a betaalphabeta subdomain that exhibits significant conformational flexibility as it accommodates inhibitor binding. CHIR-090 displays a 27 mm zone of inhibition against Y. enterocolitica in a Kirby-Bauer antibiotic assay, which is comparable to its reported activity against other Gram-negative species including E. coli and Pseudomonas aeruginosa. This study demonstrates that the inhibition of LpxC should be explored as a potential therapeutic and/or prophylatic response to infection by weaponized Yersinia species.

Structure of the Metal-Dependent Deacetylase LpxC from Yersinia enterocolitica Complexed with the Potent Inhibitor CHIR-090 .,Cole KE, Gattis SG, Angell HD, Fierke CA, Christianson DW Biochemistry. 2010 Dec 20. PMID:21171638<ref>PMID:21171638</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3nzk" style="background-color:#fffaf0;"></div>

==See Also==
*[[UDP-3-O-acyl-N-acetylglucosamine deacetylase|UDP-3-O-acyl-N-acetylglucosamine deacetylase]]
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Yersinia enterocolitica]]
[[Category: Christianson DW]]
[[Category: Cole KE]]