An experimental and computational investigation of spontaneous lasso formation in microcin J25.

ABSTRACT: The antimicrobial peptide microcin J25 (MccJ25) is posttranslationally matured from a linear preprotein into its native lasso conformation by two enzymes. One of these enzymes cleaves the preprotein and the second enzyme installs the requisite isopeptide bond to establish the lasso structure. Analysis of a mimic of MccJ25 that can be cyclized without the influence of the maturation enzymes suggests that MccJ25 does not spontaneously adopt a near-lasso structure. In addition, we conducted atomistically detailed replica-exchange molecular dynamics simulations of pro-microcin J25 (pro-MccJ25), the 21-residue uncyclized analog of MccJ25, to determine the conformational ensemble explored in the absence of the leader sequence or maturation enzymes. We applied a nonlinear dimensionality reduction

SUBMITTER: Ferguson AL 

PROVIDER: S-EPMC2965945 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature