4WP3

Crystal Structure of Adenylyl cyclase from Mycobacterium avium Ma1120 wild type

4WP3 の概要

• エントリーDOI: 10.2210/pdb4wp3/pdb
• 関連するPDBエントリー: 4WP8 4WP9 4WPA
• 分子名称: Ma1120, CHLORIDE ION (3 entities in total)
• 機能のキーワード: adenylyl cyclase, lyase
• 由来する生物種: Mycobacterium avium
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 139488.95

構造登録者

Barathy, D.V.,Bharambe, N.G.,Suguna, K. (登録日: 2014-10-17, 公開日: 2015-09-02, 最終更新日: 2023-11-08)

主引用文献

Barathy, D.V.,Bharambe, N.G.,Syed, W.,Zaveri, A.,Visweswariah, S.S.,Cola sigmaf o, M.,Misquith, S.,Suguna, K.
Autoinhibitory mechanism and activity-related structural changes in a mycobacterial adenylyl cyclase
J.Struct.Biol., 190:304-313, 2015

PubMed Abstract: An adenylyl cyclase from Mycobacterium avium, Ma1120, is a functional orthologue of a pseudogene Rv1120c from Mycobacterium tuberculosis. We report the crystal structure of Ma1120 in a monomeric form and its truncated construct as a dimer. Ma1120 exists as a monomer in solution and crystallized as a monomer in the absence of substrate or inhibitor. An additional α-helix present at the N-terminus of the monomeric structure blocks the active site by interacting with the substrate binding residues and occupying the dimer interface region. However, the enzyme has been found to be active in solution, indicating the movement of the helix away from the interface to facilitate the formation of active dimers in conditions favourable for catalysis. Thus, the N-terminal helix of Ma1120 keeps the enzyme in an autoinhibited state when it is not active. Deletion of this helix enabled us to crystallize the molecule as an active homodimer in the presence of a P-site inhibitor 2',5'-dideoxy-3'-ATP, or pyrophosphate along with metal ions. The substrate specifying lysine residue plays a dual role of interacting with the substrate and stabilizing the dimer. The dimerization loop region harbouring the second substrate specifying residue, an aspartate, shows significant differences in conformation and position between the monomeric and dimeric structures. Thus, this study has not only revealed that significant structural transitions are required for the interconversion of the inactive and the active forms of the enzyme, but also provided precise nature of these transitions.

PubMed: 25916753
DOI: 10.1016/j.jsb.2015.04.013

実験手法

X-RAY DIFFRACTION (1.95 Å)