5YRP

Crystal structure of the EAL domain of Mycobacterium smegmatis DcpA

5YRP の概要

• エントリーDOI: 10.2210/pdb5yrp/pdb
• 分子名称: Sensory box/response regulator, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: c-di-gmp, diguanylate cyclase, phosphodiesterase, gaf, biosynthetic protein
• 由来する生物種: Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 53347.15

構造登録者

Chen, H.J.,li, N.,Luo, Y.,Jiang, Y.L.,Zhou, C.Z.,Chen, Y.,Li, Q. (登録日: 2017-11-09, 公開日: 2018-05-09, 最終更新日: 2024-11-06)

主引用文献

Chen, H.J.,Li, N.,Luo, Y.,Jiang, Y.L.,Zhou, C.Z.,Chen, Y.,Li, Q.
The GDP-switched GAF domain of DcpA modulates the concerted synthesis/hydrolysis of c-di-GMP inMycobacterium smegmatis.
Biochem. J., 475:1295-1308, 2018

PubMed Abstract: The second messenger c-di-GMP [bis-(3'-5')-cyclic dimeric guanosine monophosphate] plays a key role in bacterial growth, survival and pathogenesis, and thus its intracellular homeostasis should be finely maintained. encodes a GAF (mammalian cMP-regulated phosphodiesterases, denylyl cyclases and transcription activator hlA) domain containing bifunctional enzyme DcpA (iguanylate yclase and hosphodiesterase ) that catalyzes the synthesis and hydrolysis of c-di-GMP Here, we found that DcpA catalyzes the hydrolysis of c-di-GMP at a higher velocity, compared with synthetic activity, resulting in a sum reaction from the ultimate substrate GTP to the final product pGpG [5'-phosphoguanylyl-(3'-5')-guanosine]. Fusion with the N-terminal GAF domain enables the GGDEF (Gly-Gly-Asp-Glu-Phe) domain of DcpA to dimerize and accordingly gain synthetic activity. Screening of putative metabolites revealed that GDP is the ligand of the GAF domain. Binding of GDP to the GAF domain down-regulates synthetic activity, but up-regulates hydrolytic activity, which, in consequence, might enable a timely response to the transient accumulation of c-di-GMP at the stationary phase or under stresses. Combined with the crystal structure of the EAL (Glu-Ala-Leu) domain and the small-angle X-ray scattering data, we propose a putative regulatory model of the GAF domain finely tuned by the intracellular GTP/GDP ratio. These findings help us to better understand the concerted control of the synthesis and hydrolysis of c-di-GMP in in various microenvironments.

PubMed: 29555845
DOI: 10.1042/BCJ20180079

実験手法

X-RAY DIFFRACTION (2.99 Å)