Lasso peptides

from Wikipedia, the free encyclopedia
3D structure of Microcin J25. For the sake of clarity, only the backbone atoms and the side chain of glutamate are shown. The coloring gives information about the spatial position of the atoms (red: in front, blue: behind).

Lasso peptides are 16 to 21 amino acid , long ribosomally synthesized and post-translationally modified peptides with very different biological functions, but which have one structural commonality.

3D structure

The free amino group of the first amino acid ( glycine or cysteine ) forms a peptide bond to an aspartate or glutamate side chain in position 8 or 9, thereby creating a lactam ring . The tail, comprising 7 to 13 amino acids, is passed through this ring. Usually this tail is sterically fixed by large remnants on both sides of the ring. This unusual structure, which is thermally stable as well as against proteolysis, gave this peptide group its name, which only includes a few representatives. The lasso peptides whose 3D structure is not yet known are included in this group due to the similarities in the amino acid sequence and their stability, even if this assignment has not been finally confirmed.

Structure of the gene clusters

The associated gene clusters of some lasso peptides have been sequenced. In principle, such a gene cluster consists of 4 open reading frames . The genes McjA, McjB, McjC and McjD were named for the gene cluster of Microcin J25 that has been best investigated to date. Gene A codes for the precursor peptide, which is processed by enzymes B and C to form the lasso peptide and is exported by transporter D. The precursor peptides are 40 to 60 amino acids long and have the sequence found in the native lasso peptide at the C terminus. BLAST searches have shown similarities between enzyme B and transglutaminases or proteases , so it is very likely involved in the cleavage of the precursor peptide. Enzyme C shares similarities with class B asparagine synthetases and β-lactam synthetases and is therefore likely responsible for the formation of the ring. Protein D has homologies with ABC (ATP-Binding-Casette) transporters and is involved in the export of the lasso peptide from the cell.

The lasso peptides known so far are listed in the following table. The amino acids that close the lactam ring are in bold, cysteine ​​residues that form disulfide bridges are in italics.

Surname sequence Peptide length 3D structure known Producing organism
Microcin J25 G GAGHVP E YFVGIGTPISFYG 21 (1-8) Yes Escherichia coli
Anantine G FIGWGN D IFGHYSGDF 17 (1-8) No Streptomyces sp.
Capistruin G TPGFQTP D ARVISRFGFN 19 (1-9) Yes Burkholderia sp.
Lariate A G SQLVYR E WVGHSNVIKP 18 (1-8) Yes Rhodococcus sp.
Lariatin B G SQLVYR E WVGHSNVIKGPP 20 (1-8) Yes Rhodococcus sp.
Propeptin I. G YPWWDYR D LFGGHTFISP 19 (1-9) No Microbispora sp.
Propeptin II G YPWWDYR D LFGGHTFI 17 (1-9) No Microbispora sp.
RES 701-1 G NWHGTAP D WFFNYYW 16 (1-9) No Streptomyces sp.
RES 701-3 G NWHGTSP D WFFNYYW 16 (1-9) No Streptomyces sp.
Aborycin C LGIGS C N D FAG C GYAVV C FW 21 (1-9) Yes Streptomyces sp.
Syamicin I. C LGVGS C N D FAG C GYAIV C FW 21 (1-9) No Streptomyces sp.

swell

  1. ↑ Craik et al. JACS, 2003, 125 (41): 12464-12474
  2. ↑ Wyss et al. J. antibiotics, 1991, 4 (2): 172-180
  3. ↑ Knappe et al. JACS, 2008, 130 (34): 11446-11454
  4. ↑ Iwatsuki et al. JACS, 2006, 128 (23): 7486-7491
  5. ↑ Kimura et al. J. antibiotics, 1996, 50 (5): 373-378
  6. ↑ Morishita et al. J. antibiotics, 1993, 47 (3): 269-275
  7. ↑ Ogawa et al. J. antibiotics, 1995, 48 (11): 1213-1220
  8. ↑ Helynck et al. J. antibiotics, 1993, 46 (11): 1756-1757
  9. ↑ Yamasaki et al. B. & M. Chem., 1996, 4 (1): 115-120