2ves

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[[Image:2ves.jpg|left|200px]]
 
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{{Structure
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==Crystal Structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB-78485 inhibitor==
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|PDB= 2ves |SIZE=350|CAPTION= <scene name='initialview01'>2ves</scene>, resolution 1.90&Aring;
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<StructureSection load='2ves' size='340' side='right'caption='[[2ves]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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|SITE= <scene name='pdbsite=AC1:Zn+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Zn+Binding+Site+For+Chain+B'>AC2</scene>, <scene name='pdbsite=AC3:Zn+Binding+Site+For+Chain+C'>AC3</scene>, <scene name='pdbsite=AC4:Gvr+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:Gvr+Binding+Site+For+Chain+B'>AC5</scene>, <scene name='pdbsite=AC6:Gvr+Binding+Site+For+Chain+C'>AC6</scene>, <scene name='pdbsite=AC7:Zn+Binding+Site+For+Chain+A'>AC7</scene>, <scene name='pdbsite=AC8:Zn+Binding+Site+For+Chain+B'>AC8</scene>, <scene name='pdbsite=AC9:Zn+Binding+Site+For+Chain+C'>AC9</scene>, <scene name='pdbsite=BC1:Zn+Binding+Site+For+Chain+C'>BC1</scene>, <scene name='pdbsite=BC2:So4+Binding+Site+For+Chain+B'>BC2</scene> and <scene name='pdbsite=BC3:So4+Binding+Site+For+Chain+C'>BC3</scene>
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=GVR:(2R)-N-HYDROXY-3-NAPHTHALEN-2-YL-2-[(NAPHTHALEN-2-YLSULFONYL)AMINO]PROPANAMIDE'>GVR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
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<table><tr><td colspan='2'>[[2ves]] is a 3 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=2VES OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VES FirstGlance]. <br>
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|ACTIVITY=
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#8491;</td></tr>
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|GENE=
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GVR:(2R)-N-HYDROXY-3-NAPHTHALEN-2-YL-2-[(NAPHTHALEN-2-YLSULFONYL)AMINO]PROPANAMIDE'>GVR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ves FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ves OCA], [https://pdbe.org/2ves PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ves RCSB], [https://www.ebi.ac.uk/pdbsum/2ves PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ves ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ves FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ves OCA], [http://www.ebi.ac.uk/pdbsum/2ves PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2ves RCSB]</span>
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== Function ==
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}}
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[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.
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== Evolutionary Conservation ==
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'''CRYSTAL STRUCTURE OF LPXC FROM PSEUDOMONAS AERUGINOSA COMPLEXED WITH THE POTENT BB-78485 INHIBITOR'''
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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==Overview==
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ve/2ves_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ves ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
The cell wall in Gram-negative bacteria is surrounded by an outer membrane comprised of charged lipopolysaccharide (LPS) molecules that prevent entry of hydrophobic agents into the cell and protect the bacterium from many antibiotics. The hydrophobic anchor of LPS is lipid A, the biosynthesis of which is essential for bacterial growth and viability. UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is an essential zinc-dependant enzyme that catalyzes the conversion of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine to UDP-3-O-(R-3-hydroxymyristoyl)glucosamine and acetate in the biosynthesis of lipid A, and for this reason, LpxC is an attractive target for antibacterial drug discovery. Here we disclose a 1.9 A resolution crystal structure of LpxC from Pseudomonas aeruginosa (paLpxC) in a complex with the potent BB-78485 inhibitor. To our knowledge, this is the first crystal structure of LpxC with a small-molecule inhibitor that shows antibacterial activity against a wide range of Gram-negative pathogens. Accordingly, this structure can provide important information for lead optimization and rational design of the effective small-molecule LpxC inhibitors for successful treatment of Gram-negative infections.
The cell wall in Gram-negative bacteria is surrounded by an outer membrane comprised of charged lipopolysaccharide (LPS) molecules that prevent entry of hydrophobic agents into the cell and protect the bacterium from many antibiotics. The hydrophobic anchor of LPS is lipid A, the biosynthesis of which is essential for bacterial growth and viability. UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is an essential zinc-dependant enzyme that catalyzes the conversion of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine to UDP-3-O-(R-3-hydroxymyristoyl)glucosamine and acetate in the biosynthesis of lipid A, and for this reason, LpxC is an attractive target for antibacterial drug discovery. Here we disclose a 1.9 A resolution crystal structure of LpxC from Pseudomonas aeruginosa (paLpxC) in a complex with the potent BB-78485 inhibitor. To our knowledge, this is the first crystal structure of LpxC with a small-molecule inhibitor that shows antibacterial activity against a wide range of Gram-negative pathogens. Accordingly, this structure can provide important information for lead optimization and rational design of the effective small-molecule LpxC inhibitors for successful treatment of Gram-negative infections.
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==About this Structure==
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Crystal structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB-78485 inhibitor.,Mochalkin I, Knafels JD, Lightle S Protein Sci. 2008 Mar;17(3):450-7. PMID:18287278<ref>PMID:18287278</ref>
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2VES is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_aeruginosa Pseudomonas aeruginosa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VES OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Crystal structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB-78485 inhibitor., Mochalkin I, Knafels JD, Lightle S, Protein Sci. 2008 Mar;17(3):450-7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18287278 18287278]
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</div>
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[[Category: Pseudomonas aeruginosa]]
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<div class="pdbe-citations 2ves" style="background-color:#fffaf0;"></div>
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[[Category: Single protein]]
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[[Category: Knafels, J.]]
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[[Category: Mochalkin, I.]]
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[[Category: antibiotic]]
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[[Category: bb-78485]]
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[[Category: deacetylase]]
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[[Category: gram-negative bacteria]]
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[[Category: hydrolase]]
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[[Category: hydroxamic acid]]
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[[Category: lipid a biosynthesis]]
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[[Category: lipid synthesis]]
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[[Category: lipopolysaccharide]]
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[[Category: lpxc]]
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[[Category: metalloprotease]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 05:11:22 2008''
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==See Also==
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*[[UDP-3-O-acyl-N-acetylglucosamine deacetylase|UDP-3-O-acyl-N-acetylglucosamine deacetylase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Pseudomonas aeruginosa PAO1]]
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[[Category: Knafels JD]]
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[[Category: Mochalkin I]]

Current revision

Crystal Structure of LpxC from Pseudomonas aeruginosa complexed with the potent BB-78485 inhibitor

PDB ID 2ves

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