2W01

Crystal structure of the guanylyl cyclase Cya2

2W01 の概要

• エントリーDOI: 10.2210/pdb2w01/pdb
• 分子名称: ADENYLATE CYCLASE (2 entities in total)
• 機能のキーワード: guanylyl cyclase, class iii nucleotidyl cyclase, lyase
• 由来する生物種: SYNECHOCYSTIS SP.
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 133260.34

構造登録者

Rauch, A.,Leipelt, M.,Russwurm, M.,Steegborn, C. (登録日: 2008-08-08, 公開日: 2008-09-30, 最終更新日: 2023-12-13)

主引用文献

Rauch, A.,Leipelt, M.,Russwurm, M.,Steegborn, C.
Crystal Structure of the Guanylyl Cyclase Cya2.
Proc.Natl.Acad.Sci.USA, 105:15720-, 2008

PubMed Abstract: Cyclic GMP (cGMP) is an important second messenger in eukaryotes. It is formed by guanylyl cyclases (GCs), members of the nucleotidyl cyclases class III, which also comprises adenylyl cyclases (ACs) from most organisms. To date, no structures of eukaryotic GCs are available, and all bacterial class III proteins were found to be ACs. Here we describe the biochemical and structural characterization of the class III cyclase Cya2 from cyanobacterium Synechocystis PCC6803. Cya2 shows high specificity for GTP versus ATP, revealing it to be the first bacterial GC, and sequence similarity searches indicate that GCs are also present in other bacteria. The crystal structure of Cya2 provides first structural insights into the universal GC family. Structure and mutagenesis studies show that a conserved glutamate, assisted by an interacting lysine, dominates substrate selection by forming hydrogen bonds to the substrate base. We find, however, that a second residue involved in substrate selection has an unexpected sterical role in GCs, different from its hydrogen bonding function in the related ACs. The structure identifies a tyrosine that lines the guanine binding pocket as additional residue contributing to substrate specificity. Furthermore, we find that substrate specificity stems from faster turnover of GTP, rather than different affinities for GTP and ATP, implying that the specificity-determining interactions are established after the binding step.

PubMed: 18840690
DOI: 10.1073/PNAS.0808473105

実験手法

X-RAY DIFFRACTION (2.31 Å)