1vev
From Proteopedia
|
Crystal structure of peptide deformylase from Leptospira Interrogans (LiPDF) at pH6.5
Overview
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 conformation of the CD-loop is half-open. Two pairs of Arg109-mediated cation-pi 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 peptide deformylase family. Based on our results, a novel substrate binding model, featured by an equilibrium between the closed and the open forms, is proposed. Our results present crystallographic evidence supporting population shift theory, which is distinguished from the conventional lock-and-key or induced-fit models. These results not only facilitate the development of peptide deformylase-targeted drugs but also provide structural insights into the mechanism of an unusual type of protein binding event.
About this Structure
1VEV is a Single protein structure of sequence from Leptospira interrogans with , and as ligands. Active as Peptide deformylase, with EC number 3.5.1.88 Full crystallographic information is available from OCA.
Reference
Novel conformational states of peptide deformylase from pathogenic bacterium Leptospira interrogans: implications for population shift., Zhou Z, Song X, Gong W, J Biol Chem. 2005 Dec 23;280(51):42391-6. Epub 2005 Oct 20. PMID:16239225
Page seeded by OCA on Thu Feb 21 15:34:33 2008
Categories: Leptospira interrogans | Peptide deformylase | Single protein | Gong, W. | Li, Y. | Song, X. | Zhou, Z. | FMT | MES | ZN | Closed conformation | Mes
