Novel Conformational States of Peptide Deformylase from Pathogenic Bacterium Leptospira interrogans IMPLICATIONS FOR POPULATION SHIFT *

Peptide deformylase is an attractive target for developing novel antibiotics. Previous studies at pH 3.0 showed peptide deformylase from Leptospira interrogans (LiPDF) exists as a dimer in which one monomer is in a closed form and the other is in an open form, with different conformations of the CD-loop controlling the entrance to the active pocket. Here we present structures of LiPDF at its active pH range. LiPDF forms a similar dimer at pH values 6.5–8.0 as it does at pH 3.0. Interestingly, both of the monomers are almost in the same closed form as that observed at pH 3.0. However, when the enzyme is complexed with the natural inhibitor actinotin, the con-formation of the CD-loop is half-open. Two pairs of Arg109-medi-ated cation- interactions, as well as hydrogen bonds, have been identified to stabilize the different CD-loop conformations. These results indicate that LiPDF may be found in different structural states, a feature that has never before been observed in the peptid