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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
46
|
| pubmed:dateCreated |
1997-12-19
|
| pubmed:abstractText |
The antimicrobial membrane-interacting polypeptide nisin is a prominent member of the lantibiotic family, the members of which contain thioether-bridged residues called lanthionines. To gain insight into the complex biosynthesis and the structure/function relationship of lantibiotics, the final intermediate in the biosynthesis of nisin A was studied by nuclear magnetic resonance spectroscopy. In aqueous solution the leader peptide part of this precursor adopts predominantly a random coil structure, as does the synthetic leader peptide itself. The spatial structure of the fully modified nisin part of the precursor is similar to that of nisin in water. The leader peptide part does not interact with the nisin part of the precursor molecule. Thus, these two parts of the precursor do not influence each other's conformation significantly. The conformation of the precursor was also studied while complexed to micelles of dodecylphosphocholine, mimicking the primary target of the antimicrobial activity of nisin, i.e. the cytoplasmic membrane. The location of the molecule relative to the micelles was investigated by using micelle-inserted spin-labeled 5-doxylstearic acid. It was observed that the N-terminal half of the nisin part of the precursor interacts in a different way with micelles than does the corresponding part of mature nisin, whereas no significant differences were found for the C-terminal half of the nisin part. In this model system the leader peptide is in contact with the micelles. It is concluded that the strongly reduced in vivo activity of the precursor molecule relative to that of nisin is not caused by a difference in the spatial structure of nisin and of the corresponding part of precursor nisin in water or by a shielding of the membrane interaction surface of the nisin part of the precursor by the leader peptide. Probably a different interaction of the N-terminal part of the nisin region with membranes contributes to the low activity by preventing productive insertion. The residues of the leader peptide part just next to the nisin part are likely to contribute most to the low activity of the precursor.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0006-2960
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
18
|
| pubmed:volume |
36
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
14137-45
|
| pubmed:dateRevised |
2006-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9369486-Amino Acid Sequence,
pubmed-meshheading:9369486-Anti-Bacterial Agents,
pubmed-meshheading:9369486-Molecular Sequence Data,
pubmed-meshheading:9369486-Nisin,
pubmed-meshheading:9369486-Nuclear Magnetic Resonance, Biomolecular,
pubmed-meshheading:9369486-Protein Conformation,
pubmed-meshheading:9369486-Protein Precursors,
pubmed-meshheading:9369486-Protein Sorting Signals
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Structural features of the final intermediate in the biosynthesis of the lantibiotic nisin. Influence of the leader peptide.
|
| pubmed:affiliation |
Department of Biophysical Chemistry, NIZO (Netherlands Institute for Dairy Research), Kernhemseweg 2, 6718 ZB Ede, The Netherlands.
|
| pubmed:publicationType |
Journal Article,
Comparative Study
|