3C57

Crystal Structure of the Mycobacterium tuberculosis Hypoxic Response Regulator DosR C-terminal Domain Crystal Form II

3C57 の概要

• エントリーDOI: 10.2210/pdb3c57/pdb
• 関連するPDBエントリー: 1zlj 1zlk 3C3W
• 分子名称: TWO COMPONENT TRANSCRIPTIONAL REGULATORY PROTEIN DEVR (2 entities in total)
• 機能のキーワード: response regulator, two-component regulatory system, dna-binding protein, tuberculosis, transcription regulation, transcription
• 由来する生物種: Mycobacterium tuberculosis
• 細胞内の位置: Cytoplasm (Probable): P95193
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 21028.00

構造登録者

Wisedchaisri, G.,Wu, M.,Sherman, D.R.,Hol, W.G.J. (登録日: 2008-01-30, 公開日: 2008-04-22, 最終更新日: 2023-08-30)

主引用文献

Wisedchaisri, G.,Wu, M.,Sherman, D.R.,Hol, W.G.
Crystal structures of the response regulator DosR from Mycobacterium tuberculosis suggest a helix rearrangement mechanism for phosphorylation activation
J.Mol.Biol., 378:227-242, 2008

PubMed Abstract: The response regulator DosR is essential for promoting long-term survival of Mycobacterium tuberculosis under low oxygen conditions in a dormant state and may be responsible for latent tuberculosis in one-third of the world's population. Here, we report crystal structures of full-length unphosphorylated DosR at 2.2 A resolution and its C-terminal DNA-binding domain at 1.7 A resolution. The full-length DosR structure reveals several features never seen before in other response regulators. The N-terminal domain of the full-length DosR structure has an unexpected (beta alpha)(4) topology instead of the canonical (beta alpha)(5) fold observed in other response regulators. The linker region adopts a unique conformation that contains two helices forming a four-helix bundle with two helices from another subunit, resulting in dimer formation. The C-terminal domain in the full-length DosR structure displays a novel location of helix alpha 10, which allows Gln199 to interact with the catalytic Asp54 residue of the N-terminal domain. In contrast, the structure of the DosR C-terminal domain alone displays a remarkable unstructured conformation for helix alpha 10 residues, different from the well-defined helical conformations in all other known structures, indicating considerable flexibility within the C-terminal domain. Our structures suggest a mode of DosR activation by phosphorylation via a helix rearrangement mechanism.

PubMed: 18353359
DOI: 10.1016/j.jmb.2008.02.029

実験手法

X-RAY DIFFRACTION (1.7 Å)