|
|
| Line 3: |
Line 3: |
| | <StructureSection load='6vhj' size='340' side='right'caption='[[6vhj]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | | <StructureSection load='6vhj' size='340' side='right'caption='[[6vhj]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6vhj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Promm Promm]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VHJ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VHJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6vhj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Promm Promm]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VHJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VHJ FirstGlance]. <br> |
| | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DBB:D-ALPHA-AMINOBUTYRIC+ACID'>DBB</scene></td></tr> | | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=DBB:D-ALPHA-AMINOBUTYRIC+ACID'>DBB</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vhj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vhj OCA], [http://pdbe.org/6vhj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vhj RCSB], [http://www.ebi.ac.uk/pdbsum/6vhj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vhj 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=6vhj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vhj OCA], [https://pdbe.org/6vhj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vhj RCSB], [https://www.ebi.ac.uk/pdbsum/6vhj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vhj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| - | Prochlorosins make up a class of secondary metabolites produced by strains of Prochlorococcus, single-cell, planktonic marine cyanobacteria. These polycyclic peptides contain lanthionine and methyllanthionine residues that result in thioether cross-links. In Prochlorococcus MIT9313, a single enzyme, ProcM, catalyzes the posttranslational modification of 29 linear peptide substrates to generate a library of highly diverse cyclic peptides. To investigate the catalytic promiscuity of ProcM, we chose four prochlorosins previously demonstrated to be produced by the organism for detailed structural characterization. Nuclear magnetic resonance studies allowed unambiguous assignment of the ring topologies, demonstrating a high degree of topological diversity. The stereochemistry of the lanthionine and methyllanthionine residues was determined by gas chromatography and mass spectrometry for seven prochlorosins. All methyllanthionines had the (2S,3S,6R) configuration, and the lanthionines had the (2S,6R) configuration, irrespective of the direction of cyclization, ring size, or ring topology. These findings indicate that most, if not all, of the rings in prochlorosins are formed enzymatically by ProcM lanthionine synthetase and not by a nonenzymatic process as previously suggested.
| + | Lanthipeptides are characterized by thioether crosslinks formed by post-translational modifications. The cyclization process that favors a single ring pattern over many other possible ring patterns has been the topic of much speculation. Recent studies suggest that for some systems the cyclization pattern and stereochemistry is determined not by the enzyme, but by the sequence of the precursor peptide. However, the factors that govern the outcome of the cyclization process are not understood. This study presents the three-dimensional structures of seven lanthipeptides determined by nuclear magnetic resonance spectroscopy, including five prochlorosins and the two peptides that make up cytolysin, a virulence factor produced by Enterococcus faecalis that is directly linked to human disease. These peptides were chosen because their substrate sequence determines either the ring pattern (prochlorosins) or the stereochemistry of cyclization (cytolysins). We present the structures of prochlorosins 1.1, 2.1, 2.8, 2.10 and 2.11, the first three-dimensional structures of prochlorosins. Our findings provide insights into the molecular determinants of cyclization as well as why some prochlorosins may be better starting points for library generation than others. The structures of the large and small subunits of the enterococcal cytolysin show that these peptides have long helical stretches, a rare observation for lanthipeptides characterized to date. These helices may explain their pore forming activity and suggest that the small subunit may recognize a molecular target followed by recruitment of the large subunit to span the membrane. |
| | | | |
| - | Structural characterization of four prochlorosins: a novel class of lantipeptides produced by planktonic marine cyanobacteria.,Tang W, van der Donk WA Biochemistry. 2012 May 29;51(21):4271-9. doi: 10.1021/bi300255s. Epub 2012 May, 17. PMID:22574919<ref>PMID:22574919</ref> | + | Structural determinants of macrocyclization in substrate-controlled lanthipeptide biosynthetic pathways.,Bobeica SC, Zhu L, Acedo JZ, Tang W, van der Donk WA Chem Sci. 2020 Jun 25;11(47):12854-12870. doi: 10.1039/d0sc01651a. PMID:34094481<ref>PMID:34094481</ref> |
| | | | |
| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| Structural highlights
Publication Abstract from PubMed
Lanthipeptides are characterized by thioether crosslinks formed by post-translational modifications. The cyclization process that favors a single ring pattern over many other possible ring patterns has been the topic of much speculation. Recent studies suggest that for some systems the cyclization pattern and stereochemistry is determined not by the enzyme, but by the sequence of the precursor peptide. However, the factors that govern the outcome of the cyclization process are not understood. This study presents the three-dimensional structures of seven lanthipeptides determined by nuclear magnetic resonance spectroscopy, including five prochlorosins and the two peptides that make up cytolysin, a virulence factor produced by Enterococcus faecalis that is directly linked to human disease. These peptides were chosen because their substrate sequence determines either the ring pattern (prochlorosins) or the stereochemistry of cyclization (cytolysins). We present the structures of prochlorosins 1.1, 2.1, 2.8, 2.10 and 2.11, the first three-dimensional structures of prochlorosins. Our findings provide insights into the molecular determinants of cyclization as well as why some prochlorosins may be better starting points for library generation than others. The structures of the large and small subunits of the enterococcal cytolysin show that these peptides have long helical stretches, a rare observation for lanthipeptides characterized to date. These helices may explain their pore forming activity and suggest that the small subunit may recognize a molecular target followed by recruitment of the large subunit to span the membrane.
Structural determinants of macrocyclization in substrate-controlled lanthipeptide biosynthetic pathways.,Bobeica SC, Zhu L, Acedo JZ, Tang W, van der Donk WA Chem Sci. 2020 Jun 25;11(47):12854-12870. doi: 10.1039/d0sc01651a. PMID:34094481[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Bobeica SC, Zhu L, Acedo JZ, Tang W, van der Donk WA. Structural determinants of macrocyclization in substrate-controlled lanthipeptide biosynthetic pathways. Chem Sci. 2020 Jun 25;11(47):12854-12870. doi: 10.1039/d0sc01651a. PMID:34094481 doi:http://dx.doi.org/10.1039/d0sc01651a
|
