4U0L

Structure of the Vibrio cholerae di-nucleotide cyclase (DncV) mutant D131A-D133A

4U0L の概要

• エントリーDOI: 10.2210/pdb4u0l/pdb
• 関連するPDBエントリー: 4U03 4U0M 4U0N
• 分子名称: Cyclic AMP-GMP synthase (2 entities in total)
• 機能のキーワード: regulation, mutation, transferase
• 由来する生物種: Vibrio cholerae El Tor N16961
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 95332.48

構造登録者

Xiang, Y.,Zhu, D.Y. (登録日: 2014-07-12, 公開日: 2014-09-17, 最終更新日: 2024-03-20)

主引用文献

Zhu, D.,Wang, L.,Shang, G.,Liu, X.,Zhu, J.,Lu, D.,Wang, L.,Kan, B.,Zhang, J.R.,Xiang, Y.
Structural Biochemistry of a Vibrio cholerae Dinucleotide Cyclase Reveals Cyclase Activity Regulation by Folates.
Mol.Cell, 55:931-937, 2014

PubMed Abstract: Cyclic dinucleotides are a newly expanded class of second messengers that contribute to the regulation of multiple different pathways in bacterial, eukaryotic, and archaeal cells. The recently identified Vibrio cholerae dinucleotide cyclase (DncV, the gene product of VC0179) can generate three different cyclic dinucleotides and preferentially synthesize a hybrid cyclic-GMP-AMP. Here, we report the crystal structural and functional studies of DncV. We unexpectedly observed a 5-methyltetrahydrofolate diglutamate (5MTHFGLU2) molecule bound in a surface pocket opposite the nucleotide substrate-binding groove of DncV. Subsequent mutagenesis and functional studies showed that the enzymatic activity of DncV is regulated by folate-like molecules, suggesting the existence of a signaling pathway that links folate-like metabolism cofactors to the regulation of cyclic dinucleotide second messenger synthesis. Sequence analysis showed that the residues involved in 5MTHFGLU2 binding are highly conserved in DncV orthologs, implying the presence of this regulation mechanism in a wide variety of bacteria.

PubMed: 25201413
DOI: 10.1016/j.molcel.2014.08.001

実験手法

X-RAY DIFFRACTION (2.1 Å)