6b88
From Proteopedia
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<StructureSection load='6b88' size='340' side='right' caption='[[6b88]], [[Resolution|resolution]] 2.41Å' scene=''> | <StructureSection load='6b88' size='340' side='right' caption='[[6b88]], [[Resolution|resolution]] 2.41Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6b88]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B88 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B88 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6b88]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B88 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B88 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CZD:(8S,11S,14S)-14-{[(2S)-4-amino-2-{[2-(4-tert-butylphenyl)-4-methylpyrimidine-5-carbonyl]amino}butanoyl](methyl)amino}-3,18-bis(2-aminoethoxy)-N-[(2Z)-2-iminoethyl]-11-methyl-10,13-dioxo-9,12-diazatricyclo[13.3.1.1~2,6~]icosa-1(19),2(20),3,5,15,17-hexaene-8-carboxamide'>CZD</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=CZD:(8S,11S,14S)-14-{[(2S)-4-amino-2-{[2-(4-tert-butylphenyl)-4-methylpyrimidine-5-carbonyl]amino}butanoyl](methyl)amino}-3,18-bis(2-aminoethoxy)-N-[(2Z)-2-iminoethyl]-11-methyl-10,13-dioxo-9,12-diazatricyclo[13.3.1.1~2,6~]icosa-1(19),2(20),3,5,15,17-hexaene-8-carboxamide'>CZD</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lepB, b2568, JW2552 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Signal_peptidase_I Signal peptidase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.89 3.4.21.89] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Signal_peptidase_I Signal peptidase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.89 3.4.21.89] </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=6b88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b88 OCA], [http://pdbe.org/6b88 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b88 RCSB], [http://www.ebi.ac.uk/pdbsum/6b88 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b88 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=6b88 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b88 OCA], [http://pdbe.org/6b88 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b88 RCSB], [http://www.ebi.ac.uk/pdbsum/6b88 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b88 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Multidrug-resistant bacteria are spreading at alarming rates, and despite extensive efforts no new class of antibiotic with activity against Gram-negative bacteria has been approved in over fifty years. Natural products and their derivatives have a key role in combating Gram-negative pathogens. Here we report chemical optimization of the arylomycins-a class of natural products with weak activity and limited spectrum-to obtain G0775, a molecule with potent, broad-spectrum activity against Gram-negative bacteria. G0775 inhibits the essential bacterial type I signal peptidase, a new antibiotic target, through an unprecedented molecular mechanism. It circumvents existing antibiotic resistance mechanisms and retains activity against contemporary multidrug-resistant Gram-negative clinical isolates in vitro and in several in vivo infection models. These findings demonstrate that optimized arylomycin analogues such as G0775 could translate into new therapies to address the growing threat of multidrug-resistant Gram-negative infections. | ||
| + | |||
| + | Optimized arylomycins are a new class of Gram-negative antibiotics.,Smith PA, Koehler MFT, Girgis HS, Yan D, Chen Y, Chen Y, Crawford JJ, Durk MR, Higuchi RI, Kang J, Murray J, Paraselli P, Park S, Phung W, Quinn JG, Roberts TC, Rouge L, Schwarz JB, Skippington E, Wai J, Xu M, Yu Z, Zhang H, Tan MW, Heise CE Nature. 2018 Sep;561(7722):189-194. doi: 10.1038/s41586-018-0483-6. Epub 2018 Sep, 12. PMID:30209367<ref>PMID:30209367</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6b88" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Ecoli]] | ||
[[Category: Signal peptidase I]] | [[Category: Signal peptidase I]] | ||
[[Category: Murray, J M]] | [[Category: Murray, J M]] | ||
Revision as of 06:42, 24 October 2018
E. coli LepB in complex with GNE0775 ((4S,7S,10S)-10-((S)-4-amino-2-(2-(4-(tert-butyl)phenyl)-4-methylpyrimidine-5-carboxamido)-N-methylbutanamido)-16,26-bis(2-aminoethoxy)-N-(2-iminoethyl)-7-methyl-6,9-dioxo-5,8-diaza-1,2(1,3)-dibenzenacyclodecaphane-4-carboxamide)
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