Structure of subtilosin A, an antimicrobial peptide from Bacillus subtilis with unusual posttranslational modifications linking cysteine sulfurs to alpha-carbons of phenylalanine and threonine.
The complete primary and three-dimensional solution structures of subtilosin A (1), a bacteriocin from Bacillus subtilis, were determined by multidimensional NMR studies on peptide produced using isotopically labeled [(13)C,(15)N]medium derived from Anabaena sp. grown on sodium [(13)C]bicarbonate and [(15)N]nitrate. Additional samples of 1 were also generated by separate incorporations of [U-(13)C,(15)N]phenylalanine and [U-(13)C,(15)N]threonine using otherwise unlabeled media. The results demonstrate that in addition to having a cyclized peptide backbone (N and C termini), three cross-links are formed between the sulfurs of Cys13, Cys7, and Cys4 and the alpha-positions of Phe22, Thr28, and Phe31, respectively. Such posttranslational linkage of a thiol to the alpha-carbon of an amino acid residue is very unusual in natural peptides or proteins. Subtilosin A (1) belongs to a new class of bacteriocins.
Kawulka
Karen
K
Department of Chemistry, National High Field NMR Centre, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
Sprules
Tara
T
McKay
Ryan T
RT
Mercier
Pascal
P
Diaper
Christopher M
CM
Zuber
Peter
P
Vederas
John C
JC
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism*; D001412:Bacillus subtilis / Q000378:metabolism*; D001426:Bacterial Proteins; D001430:Bacteriocins; D003545:Cysteine / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides; D010456:Peptides, Cyclic; D010649:Phenylalanine / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D013912:Threonine / Q000378:metabolism
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D010455:Peptides; D010456:Peptides, Cyclic; D013912:Threonine; D010649:Phenylalanine; C047828:sboA protein, Bacillus subtilis; D003545:Cysteine