Structure of microcin J25, a peptide inhibitor of bacterial RNA polymerase, is a lassoed tail.
Microcin J25 (MccJ25) is a 21-amino acid peptide inhibitor active against the DNA-dependent RNA polymerase of Gram negative bacteria. Previously, the structure of MccJ25 was reported to be a head-to-tail circle, cyclo(-G(1)GAGHVPEYF(10)VGIGTPISFY(20)G-). On the basis of biochemical studies, mass spectrometry, and NMR, we show that this structure is incorrect, and that the peptide has an extraordinary structural fold. MccJ25 contains an internal lactam linkage between the alpha-amino group of Gly1 and the gamma-carboxyl of Glu8. The tail (Tyr9-Gly21) passes through the ring (Gly1-Glu8), with Phe19 and Tyr20 straddling each side of the ring, sterically trapping the tail in a noncovalent interaction we call a lassoed tail.
Wilson
Kelly-Anne
KA
Laboratory of Molecular Biophysics, The Rockefeller University, New York, New York 10021, USA.
Kalkum
Markus
M
Ottesen
Jennifer
J
Yuzenkova
Julia
J
Chait
Brian T
BT
Landick
Robert
R
Muir
Tom
T
Severinov
Konstantin
K
Darst
Seth A
SA
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001430:Bacteriocins / Q000737:chemistry* / Q000494:pharmacology; D012321:DNA-Directed RNA Polymerases / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D010456:Peptides, Cyclic; C020411:microcin; D012321:DNA-Directed RNA Polymerases