3QQA

Crystal structures of CmeR-bile acid complexes from Campylobacter jejuni

3QQA の概要

• エントリーDOI: 10.2210/pdb3qqa/pdb
• 関連するPDBエントリー: 3OQU 3QPS
• 分子名称: CmeR, TAUROCHOLIC ACID (3 entities in total)
• 機能のキーワード: alpha-helical, helix-turn-helix, dna-binding, transcription regulation, transcription repressor, drug binding, transcription
• 由来する生物種: Campylobacter jejuni
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 25607.48

構造登録者

Lei, H.T.,Routh, M.D.,Shen, Z.,Su, C.-C.,Zhang, Q.,Yu, E.W. (登録日: 2011-02-15, 公開日: 2011-03-16, 最終更新日: 2024-02-21)

主引用文献

Lei, H.T.,Shen, Z.,Surana, P.,Routh, M.D.,Su, C.C.,Zhang, Q.,Yu, E.W.
Crystal structures of CmeR-bile acid complexes from Campylobacter jejuni.
Protein Sci., 20:712-723, 2011

PubMed Abstract: The TetR family of transcription regulators are diverse proteins capable of sensing and responding to various structurally dissimilar antimicrobial agents. Upon detecting these agents, the regulators allow transcription of an appropriate array of resistance markers to counteract the deleterious compounds. Campylobacter jejuni CmeR is a pleiotropic regulator of multiple proteins, including the membrane-bound multidrug efflux transporter CmeABC. CmeR represses the expression of CmeABC and is induced by bile acids, which are substrates of the CmeABC tripartite pump. The multiligand-binding pocket of CmeR has been shown to be very extensive and consists of several positively charged and multiple aromatic amino acids. Here we describe the crystal structures of CmeR in complexes with the bile acids, taurocholate and cholate. Taurocholate and cholate are structurally related, differing by only the anionic charged group. However, these two ligands bind distinctly in the binding tunnel. Taurocholate spans the novel bile acid binding site adjacent to and without overlapping with the previously determined glycerol-binding site. The anionic aminoethanesulfonate group of taurocholate is neutralized by a charge-dipole interaction. Unlike taurocholate, cholate binds in an anti-parallel orientation but occupies the same bile acid-binding site. Its anionic pentanoate moiety makes a water-mediated hydrogen bond with a cationic residue to neutralize the formal negative charge. These structures underscore the promiscuity of the multifaceted binding pocket of CmeR. The capacity of CmeR to recognize bile acids was confirmed using isothermal titration calorimetry and fluorescence polarization. The results revealed that the regulator binds these acids with dissociation constants in the micromolar region.

PubMed: 21328631
DOI: 10.1002/pro.602

実験手法

X-RAY DIFFRACTION (2.2 Å)