1VEV

Crystal structure of peptide deformylase from Leptospira Interrogans (LiPDF) at pH6.5

1VEV の概要

• エントリーDOI: 10.2210/pdb1vev/pdb
• 関連するPDBエントリー: 1RN5 1SV2 1VEY 1VEZ
• 分子名称: Peptide deformylase, ZINC ION, 2-(N-MORPHOLINO)-ETHANESULFONIC ACID, ... (5 entities in total)
• 機能のキーワード: closed conformation, mes, hydrolase
• 由来する生物種: Leptospira interrogans
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 41356.81

構造登録者

Zhou, Z.,Song, X.,Li, Y.,Gong, W. (登録日: 2004-04-06, 公開日: 2005-08-23, 最終更新日: 2023-10-25)

主引用文献

Zhou, Z.,Song, X.,Gong, W.
Novel conformational states of peptide deformylase from pathogenic bacterium Leptospira interrogans: implications for population shift
J.Biol.Chem., 280:42391-42396, 2005

PubMed Abstract: 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.

PubMed: 16239225
DOI: 10.1074/jbc.M506370200

実験手法

X-RAY DIFFRACTION (2.51 Å)