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5drq

From Proteopedia

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Crystal structure of the Pseudomonas aeruginosa LpxC/LPC-040 complex

Structural highlights

5drq is a 1 chain structure with sequence from Pseudomonas aeruginosa PAO1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.63Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LPXC_PSEAE Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.

Publication Abstract from PubMed

Conformational dynamics plays an important role in enzyme catalysis, allosteric regulation of protein functions and assembly of macromolecular complexes. Despite these well-established roles, such information has yet to be exploited for drug design. Here we show by nuclear magnetic resonance spectroscopy that inhibitors of LpxC-an essential enzyme of the lipid A biosynthetic pathway in Gram-negative bacteria and a validated novel antibiotic target-access alternative, minor population states in solution in addition to the ligand conformation observed in crystal structures. These conformations collectively delineate an inhibitor envelope that is invisible to crystallography, but is dynamically accessible by small molecules in solution. Drug design exploiting such a hidden inhibitor envelope has led to the development of potent antibiotics with inhibition constants in the single-digit picomolar range. The principle of the cryptic inhibitor envelope approach may be broadly applicable to other lead optimization campaigns to yield improved therapeutics.

Drug design from the cryptic inhibitor envelope.,Lee CJ, Liang X, Wu Q, Najeeb J, Zhao J, Gopalaswamy R, Titecat M, Sebbane F, Lemaitre N, Toone EJ, Zhou P Nat Commun. 2016 Feb 25;7:10638. doi: 10.1038/ncomms10638. PMID:26912110^[1]

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

References

↑ Lee CJ, Liang X, Wu Q, Najeeb J, Zhao J, Gopalaswamy R, Titecat M, Sebbane F, Lemaitre N, Toone EJ, Zhou P. Drug design from the cryptic inhibitor envelope. Nat Commun. 2016 Feb 25;7:10638. doi: 10.1038/ncomms10638. PMID:26912110 doi:http://dx.doi.org/10.1038/ncomms10638

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5drq"

Categories: Large Structures | Pseudomonas aeruginosa PAO1 | Lee C-J | Najeeb J | Zhou P

@@ Line 3: / Line 3: @@
 <StructureSection load='5drq' size='340' side='right'caption='[[5drq]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5drq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Pseae Pseae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DRQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5DRQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5drq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_aeruginosa_PAO1 Pseudomonas aeruginosa PAO1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5DRQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DRQ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5EM:N-[(2S)-3-AMINO-1-(HYDROXYAMINO)-3-METHYL-1-OXOBUTAN-2-YL]-4-[4-(4-AMINOPHENYL)BUTA-1,3-DIYN-1-YL]BENZAMIDE'>5EM</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</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">X-ray diffraction, [[Resolution|Resolution]] 1.63&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5dro|5dro]], [[5drp|5drp]], [[5drr|5drr]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5EM:N-[(2S)-3-AMINO-1-(HYDROXYAMINO)-3-METHYL-1-OXOBUTAN-2-YL]-4-[4-(4-AMINOPHENYL)BUTA-1,3-DIYN-1-YL]BENZAMIDE'>5EM</scene>, <scene name='pdbligand=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lpxC, envA, PA4406 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=208964 PSEAE])</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=5drq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5drq OCA], [https://pdbe.org/5drq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5drq RCSB], [https://www.ebi.ac.uk/pdbsum/5drq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5drq ProSAT]</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=5drq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5drq OCA], [http://pdbe.org/5drq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5drq RCSB], [http://www.ebi.ac.uk/pdbsum/5drq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5drq ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/LPXC_PSEAE LPXC_PSEAE]] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.
+[https://www.uniprot.org/uniprot/LPXC_PSEAE LPXC_PSEAE] Involved in the biosynthesis of lipid A, a phosphorylated glycolipid that anchors the lipopolysaccharide to the outer membrane of the cell.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 28: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Pseae]]
+[[Category: Pseudomonas aeruginosa PAO1]]
-[[Category: Lee, C J]]
+[[Category: Lee C-J]]
-[[Category: Najeeb, J]]
+[[Category: Najeeb J]]
-[[Category: Zhou, P]]
+[[Category: Zhou P]]
-[[Category: Gram-negative bacteria]]
-[[Category: Hydrolase-hydrolase inhibitor complex]]
-[[Category: Inhibitor]]
-[[Category: Lipid some]]
-[[Category: Lpxc]]

5drq

From Proteopedia

Current revision

Crystal structure of the Pseudomonas aeruginosa LpxC/LPC-040 complex

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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