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2jt2

From Proteopedia

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Current revision

Solution Structure of the Aquifex aeolicus LpxC- CHIR-090 complex

Structural highlights

2jt2 is a 1 chain structure with sequence from Aquifex aeolicus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LPXC_AQUAE Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell (By similarity).

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 UDP-3-O-(R-3-hydroxyacyl)-N-acetylglucosamine deacetylase LpxC is an essential enzyme of lipid A biosynthesis in Gram-negative bacteria and a promising antibiotic target. CHIR-090, the most potent LpxC inhibitor discovered to date, displays two-step time-dependent inhibition and kills a wide range of Gram-negative pathogens as effectively as ciprofloxacin or tobramycin. In this study, we report the solution structure of the LpxC-CHIR-090 complex. CHIR-090 exploits conserved features of LpxC that are critical for catalysis, including the hydrophobic passage and essential active-site residues. CHIR-090 is adjacent to, but does not occupy, the UDP-binding pocket of LpxC, suggesting that a fragment-based approach may facilitate further optimization of LpxC inhibitors. Additionally, we identified key residues in the Insert II hydrophobic passage that modulate time-dependent inhibition and CHIR-090 resistance. CHIR-090 shares a similar, although previously unrecognized, chemical scaffold with other small-molecule antibiotics such as L-161,240 targeting LpxC, and provides a template for understanding the binding mode of these inhibitors. Consistent with this model, we provide evidence that L-161,240 also occupies the hydrophobic passage.

Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligand binding.,Barb AW, Jiang L, Raetz CR, Zhou P Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18433-8. Epub 2007 Nov 19. PMID:18025458^[1]

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

References

↑ Barb AW, Jiang L, Raetz CR, Zhou P. Structure of the deacetylase LpxC bound to the antibiotic CHIR-090: Time-dependent inhibition and specificity in ligand binding. Proc Natl Acad Sci U S A. 2007 Nov 20;104(47):18433-8. Epub 2007 Nov 19. PMID:18025458

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/2jt2"

@@ Line 1: / Line 1: @@
 ==Solution Structure of the Aquifex aeolicus LpxC- CHIR-090 complex==
-<StructureSection load='2jt2' size='340' side='right'caption='[[2jt2]], [[NMR_Ensembles_of_Models | 25 NMR models]]' scene=''>
+<StructureSection load='2jt2' size='340' side='right'caption='[[2jt2]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2jt2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"aquifex_aeolicus"_huber_and_stetter_2001 "aquifex aeolicus" huber and stetter 2001]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JT2 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2jt2]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JT2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JT2 FirstGlance]. <br>
-</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=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpxC, envA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=63363 "Aquifex aeolicus" Huber and Stetter 2001])</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=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=2jt2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jt2 OCA], [https://pdbe.org/2jt2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jt2 RCSB], [https://www.ebi.ac.uk/pdbsum/2jt2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jt2 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[https://www.uniprot.org/uniprot/LPXC_AQUAE LPXC_AQUAE]] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell (By similarity).
+[https://www.uniprot.org/uniprot/LPXC_AQUAE LPXC_AQUAE] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell (By similarity).
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 32: @@
 ==See Also==
 *[[UDP-3-O-acyl-N-acetylglucosamine deacetylase|UDP-3-O-acyl-N-acetylglucosamine deacetylase]]
+*[[UDP-3-O-acyl-N-acetylglucosamine deacetylase 3D structures|UDP-3-O-acyl-N-acetylglucosamine deacetylase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Aquifex aeolicus huber and stetter 2001]]
+[[Category: Aquifex aeolicus]]
 [[Category: Large Structures]]
-[[Category: Barb, A W]]
+[[Category: Barb AW]]
-[[Category: Jiang, L]]
+[[Category: Jiang L]]
-[[Category: Raetz, C R.H]]
+[[Category: Raetz CRH]]
-[[Category: Zhou, P]]
+[[Category: Zhou P]]
-[[Category: Antibiotic]]
-[[Category: Chir-090]]
-[[Category: Hydrolase]]
-[[Category: Hydroxamate]]
-[[Category: Lipid some]]
-[[Category: Lipid a biosynthesis]]
-[[Category: Lipid synthesis]]

2jt2

From Proteopedia

Current revision

Solution Structure of the Aquifex aeolicus LpxC- CHIR-090 complex

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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