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| | <StructureSection load='3s04' size='340' side='right'caption='[[3s04]], [[Resolution|resolution]] 2.44Å' scene=''> | | <StructureSection load='3s04' size='340' side='right'caption='[[3s04]], [[Resolution|resolution]] 2.44Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3s04]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Ecoli Ecoli] and [https://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S04 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3s04]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3S04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3S04 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=02U:14-METHYLHEXADEC-9-ENOIC+ACID'>02U</scene>, <scene name='pdbligand=RAM:ALPHA-L-RHAMNOSE'>RAM</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]] 2.44Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=02V:(2S)-(3,4-DIHYDROXYPHENYL)(METHYLAMINO)ETHANOIC+ACID'>02V</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DSE:N-METHYL-D-SERINE'>DSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=02U:14-METHYLHEXADEC-9-ENOIC+ACID'>02U</scene>, <scene name='pdbligand=02V:(2S)-(3,4-DIHYDROXYPHENYL)(METHYLAMINO)ETHANOIC+ACID'>02V</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DSE:N-METHYL-D-SERINE'>DSE</scene>, <scene name='pdbligand=RAM:ALPHA-L-RHAMNOSE'>RAM</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1b12|1b12]], [[1t7d|1t7d]], [[3iiq|3iiq]], [[1kn9|1kn9]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">b2568, JW2552, lepB ([https://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'>[https://en.wikipedia.org/wiki/Signal_peptidase_I Signal peptidase I], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3s04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s04 OCA], [https://pdbe.org/3s04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s04 RCSB], [https://www.ebi.ac.uk/pdbsum/3s04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s04 ProSAT]</span></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=3s04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3s04 OCA], [https://pdbe.org/3s04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3s04 RCSB], [https://www.ebi.ac.uk/pdbsum/3s04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3s04 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LEP_ECOLI LEP_ECOLI] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Signal peptidase I]] | |
| | [[Category: Streptomyces sp]] | | [[Category: Streptomyces sp]] |
| - | [[Category: Luo, C]] | + | [[Category: Luo C]] |
| - | [[Category: Paetzel, M]] | + | [[Category: Paetzel M]] |
| - | [[Category: Cytoplasmic membrane]]
| + | |
| - | [[Category: Hydrolase-antibiotic complex]]
| + | |
| - | [[Category: Leader peptidase]]
| + | |
| - | [[Category: Leader peptide]]
| + | |
| - | [[Category: Membrane bound]]
| + | |
| - | [[Category: Mostly-beta fold]]
| + | |
| - | [[Category: Secreted preprotein]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Serine-lysine dyad]]
| + | |
| - | [[Category: Signal peptidase]]
| + | |
| - | [[Category: Signal peptide]]
| + | |
| Structural highlights
3s04 is a 4 chain structure with sequence from Escherichia coli K-12 and Streptomyces sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.44Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
LEP_ECOLI
Publication Abstract from PubMed
Glycosylation of natural products, including antibiotics, often plays an important role in determining their physical properties and their biological activity, and thus their potential as drug candidates. The arylomycin class of antibiotics inhibits bacterial type I signal peptidase and is comprised of three related series of natural products with a lipopeptide tail attached to a core macrocycle. Previously, we reported the total synthesis of several A series derivatives, which have unmodified core macrocycles, as well as B series derivatives, which have a nitrated macrocycle. We now report the synthesis and biological evaluation of lipoglycopeptide arylomycin variants whose macrocycles are glycosylated with a deoxy-alpha-mannose substituent, and also in some cases hydroxylated. The synthesis of the derivatives bearing each possible deoxy-alpha-mannose enantiomer allowed us to assign the absolute stereochemistry of the sugar in the natural product and also to show that while glycosylation does not alter antibacterial activity, it does appear to improve solubility. Crystallographic structural studies of a lipoglycopeptide arylomycin bound to its signal peptidase target reveal the molecular interactions that underlie inhibition and also that the mannose is directed away from the binding site into solvent which suggests that other modifications may be made at the same position to further increase solubility and thus reduce protein binding and possibly optimize the pharmacokinetics of the scaffold.
Synthesis and Characterization of the Arylomycin Lipoglycopeptide Antibiotics and the Crystallographic Analysis of Their Complex with Signal Peptidase.,Liu J, Luo C, Smith PA, Chin JK, Page MG, Paetzel M, Romesberg FE J Am Chem Soc. 2011 Oct 14. PMID:21999324[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Liu J, Luo C, Smith PA, Chin JK, Page MG, Paetzel M, Romesberg FE. Synthesis and Characterization of the Arylomycin Lipoglycopeptide Antibiotics and the Crystallographic Analysis of Their Complex with Signal Peptidase. J Am Chem Soc. 2011 Oct 14. PMID:21999324 doi:10.1021/ja207318n
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