1Q71

The structure of microcin J25 is a threaded sidechain-to-backbone ring structure and not a head-to-tail cyclized backbone

Summary for 1Q71

• Entry DOI: 10.2210/pdb1q71/pdb
• Related: 1HG6
• Related PRD ID: PRD_000184
• Descriptor: microcin J25 (1 entity in total)
• Functional Keywords: microcin j25, mccj25, sidechain-to-backbone link, antimicrobial peptide, antimicrobial protein, antibiotic
• Biological source: Escherichia coli
• Cellular location: Secreted: Q9X2V7
• Total number of polymer chains: 1
• Total formula weight: 2126.35

Authors

Rosengren, K.J.,Clark, R.,Daly, N.L.,Goransson, U.,Jones, A.,Craik, D.J. (deposition date: 2003-08-14, release date: 2003-12-16, Last modification date: 2012-12-12)

Primary citation

Rosengren, K.J.,Clark, R.J.,Daly, N.L.,Goransson, U.,Jones, A.,Craik, D.J.
Microcin J25 has a threaded sidechain-to-backbone ring structure and not a head-to-tail cyclized backbone.
J.Am.Chem.Soc., 125:12464-12474, 2003

PubMed Abstract: Microcin J25 is a 21 amino acid bacterial peptide that has potent antibacterial activity against Gram-negative bacteria, resulting from its interaction with RNA polymerase. The peptide was previously proposed to have a head-to-tail cyclized peptide backbone and a tight globular structure (Blond, A., Péduzzi, J., Goulard, C., Chiuchiolo, M. J., Barthélémy, M., Prigent, Y., Salomón, R. A., Farías, R. N., Moreno, F. & Rebuffat, S. Eur. J. Biochem. 1999, 259, 747-755). It exhibits remarkable thermal stability for a peptide of its size lacking disulfide bonds and in part this was previously proposed to derive from its macrocyclic structure. We show here that in fact the peptide does not have a head-to-tail cyclic structure but rather a side chain to backbone cyclization between Glu8 and the N-terminus. This creates an embedded ring that is threaded by the C-terminal tail of the molecule, forming a noose-like feature. The three-dimensional structure deduced from NMR data suggests that slippage of the noose is prevented by two aromatic residues flanking the embedded ring. Unthreading does not occur even when the molecule is enzymatically digested with thermolysin. The new structural interpretation fully accounts for previously reported NMR and biophysical data and is consistent with the remarkable stability of this potent antimicrobial peptide.

PubMed: 14531690
DOI: 10.1021/ja0367703

Experimental method

SOLUTION NMR