2mh5: Difference between revisions
New page: '''Unreleased structure''' The entry 2mh5 is ON HOLD Authors: M nch, D., M ller, A., Schneider, T., Kohl, B., Wenzel, M., Bandow, J., Maffioli, S., Sosio, M., Donadio, S., Wimmer, R., S... |
No edit summary |
||
| (12 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==Structure and NMR assignments of lantibiotic NAI-107 in DPC micelles== | ||
<StructureSection load='2mh5' size='340' side='right'caption='[[2mh5]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2mh5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Microbispora_sp._107891 Microbispora sp. 107891]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MH5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MH5 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CW:5-CHLORO-L-TRYPTOPHAN'>5CW</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DBB:D-ALPHA-AMINOBUTYRIC+ACID'>DBB</scene>, <scene name='pdbligand=DBU:(2Z)-2-AMINOBUT-2-ENOIC+ACID'>DBU</scene>, <scene name='pdbligand=DHA:2-AMINO-ACRYLIC+ACID'>DHA</scene>, <scene name='pdbligand=DPV:DODECYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>DPV</scene>, <scene name='pdbligand=HYP:4-HYDROXYPROLINE'>HYP</scene>, <scene name='pdbligand=PRD_001219:Lantibiotic+107891'>PRD_001219</scene>, <scene name='pdbligand=TEE:2-AMINO-ETHENETHIOL'>TEE</scene></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=2mh5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mh5 OCA], [https://pdbe.org/2mh5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mh5 RCSB], [https://www.ebi.ac.uk/pdbsum/2mh5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mh5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/LAN91_MICS0 LAN91_MICS0] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The lantibiotic NAI-107 is active against Gram-positive bacteria including vancomycin resistant enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA). To identify the molecular basis of its potency, we studied the mode of action in a series of whole cell and in vitro assays and analyzed structural features by nuclear magnetic resonance. The lantibiotic efficiently interfered with late stages of cell biosynthesis and induced accumulation of the soluble peptidoglycan precursor UDP-N- acetylmuramic acid-pentapeptide (UDP-MurNAc-pentapeptide) in the cytoplasm. Using membrane preparations and a complete cascade of purified, recombinant late stage peptidoglycan biosynthetic enzymes (MraY, MurG, FemX, PBP2) and their respective purified substrates, we showed that NAI-107 forms complexes with bactoprenol- pyrophosphate coupled precursors of the bacterial cell wall. Titration experiments indicate that first a 1:1 stoichiometric complex occurs, which then transforms into a 2:1 (peptide : lipid II) complex, when excess peptide is added. Furthermore, lipid II and related molecules obviously could not serve as anchor molecules for the formation of defined and stable nisin-like pores, however slow membrane depolarization was observed after NAI-107 treatment, which could contribute to killing of the bacterial cell. | |||
The lantibiotic NAI-107 binds to bactoprenol bound cell wall precursors and impairs membrane functions.,Munch D, Muller A, Schneider T, Kohl B, Wenzel M, Bandow JE, Maffioli S, Sosio M, Donadio S, Wimmer R, Sahl HG J Biol Chem. 2014 Mar 13. PMID:24627484<ref>PMID:24627484</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2mh5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Microbispora sp. 107891]] | |||
[[Category: Bandow J]] | |||
[[Category: Donadio S]] | |||
[[Category: Kohl B]] | |||
[[Category: Maffioli S]] | |||
[[Category: Muller A]] | |||
[[Category: Munch D]] | |||
[[Category: Sahl H]] | |||
[[Category: Schneider T]] | |||
[[Category: Sosio M]] | |||
[[Category: Wenzel M]] | |||
[[Category: Wimmer R]] | |||
Latest revision as of 11:50, 14 July 2024
Structure and NMR assignments of lantibiotic NAI-107 in DPC micellesStructure and NMR assignments of lantibiotic NAI-107 in DPC micelles
Structural highlights
FunctionPublication Abstract from PubMedThe lantibiotic NAI-107 is active against Gram-positive bacteria including vancomycin resistant enterococci (VRE) and methicillin resistant Staphylococcus aureus (MRSA). To identify the molecular basis of its potency, we studied the mode of action in a series of whole cell and in vitro assays and analyzed structural features by nuclear magnetic resonance. The lantibiotic efficiently interfered with late stages of cell biosynthesis and induced accumulation of the soluble peptidoglycan precursor UDP-N- acetylmuramic acid-pentapeptide (UDP-MurNAc-pentapeptide) in the cytoplasm. Using membrane preparations and a complete cascade of purified, recombinant late stage peptidoglycan biosynthetic enzymes (MraY, MurG, FemX, PBP2) and their respective purified substrates, we showed that NAI-107 forms complexes with bactoprenol- pyrophosphate coupled precursors of the bacterial cell wall. Titration experiments indicate that first a 1:1 stoichiometric complex occurs, which then transforms into a 2:1 (peptide : lipid II) complex, when excess peptide is added. Furthermore, lipid II and related molecules obviously could not serve as anchor molecules for the formation of defined and stable nisin-like pores, however slow membrane depolarization was observed after NAI-107 treatment, which could contribute to killing of the bacterial cell. The lantibiotic NAI-107 binds to bactoprenol bound cell wall precursors and impairs membrane functions.,Munch D, Muller A, Schneider T, Kohl B, Wenzel M, Bandow JE, Maffioli S, Sosio M, Donadio S, Wimmer R, Sahl HG J Biol Chem. 2014 Mar 13. PMID:24627484[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||