Three-Dimensional Structure of Leucocin A in Trifluoroethanol and Dodecylphosphocholine Micelles: Spatial Location of Residues Critical for Biological Activity in Type IIa Bacteriocins from Lactic Aci
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- 作者：Nancy L. Fregeau Gallagher ; Miloslav Sailer ; Walter P. Niemczura ; Thomas T. Nakashima ; Michael E. Stiles ; and John C. Vederas
- 刊名：Biochemistry
- 出版年：1997
- 出版时间：December 9, 1997
- 年：1997
- 卷：36
- 期：49
- 页码：15062 - 15072
- 全文大小：371K
- 年卷期：v.36,no.49(December 9, 1997)
- ISSN：1520-4995
文摘
The first three-dimensional structure of a type IIa bacteriocinfrom lactic acid bacteria is reported.Complete 1H resonance assignments of leucocin A, a 37amino acid antimicrobial peptide isolated fromthe lactic acid bacterium Leuconostoc gelidum UAL187, weredetermined in 90% trifluoroethanol (TFE)-water and in aqueous dodecylphosphocholine (DPC) micelles (1:40 ratio ofleucocin A:DPC) using two-dimensional NMR techniques (e.g., DQF-COSY, TOCSY, NOESY). Circulardichroism spectra, NMRchemical shift indices, amide hydrogen exchange rates, and long-rangenuclear Overhauser effects indicatethat leucocin A adopts a reasonably well defined structure in both TFEand DPC micelle environmentsbut exists as a random coil in water or aqueous DMSO. Distancegeometry and simulated annealingcalculations were employed to generate structures for leucocin A inboth lipophilic media. While somedifferences were noted between the structures calculated for the twodifferent solvent systems, in both,the region encompassing residues 17-31 assumes an essentiallyidentical amphiphilic 
-helix conformation.A three-strand antiparallel 
-sheet domain (residues 2-16),anchored by the disulfide bridge, is alsoobserved in both media. In TFE, these two regions have a moredefined relationship relative to eachother, while, in DPC micelles, the C-terminus is folded back onto the-helix. The implications of thesestructural features with regard to the antimicrobial mechanism ofaction and target recognition are discussed.
-helix conformation.A three-strand antiparallel -sheet domain (residues 2-16),anchored by the disulfide bridge, is alsoobserved in both media. In TFE, these two regions have a moredefined relationship relative to eachother, while, in DPC micelles, the C-terminus is folded back onto the-helix. The implications of thesestructural features with regard to the antimicrobial mechanism ofaction and target recognition are discussed.