7NS8

Triphosphate tunnel metalloenzyme from Sulfolobus acidocaldarius

7NS8 の概要

• エントリーDOI: 10.2210/pdb7ns8/pdb
• 分子名称: Triphosphate tunnel metalloenzyme Saci_0718, 3-CYCLOHEXYL-1-PROPYLSULFONIC ACID, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: ttm, cyth, hydrolase
• 由来する生物種: Sulfolobus acidocaldarius (strain ATCC 33909 / DSM 639 / JCM 8929 / NBRC 15157 / NCIMB 11770)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24112.42

構造登録者

Vogt, M.S.,Essen, L.-O.,Banerjee, A. (登録日: 2021-03-05, 公開日: 2021-06-02, 最終更新日: 2024-01-31)

主引用文献

Vogt, M.S.,Ngouoko Nguepbeu, R.R.,Mohr, M.K.F.,Albers, S.V.,Essen, L.O.,Banerjee, A.
The archaeal triphosphate tunnel metalloenzyme SaTTM defines structural determinants for the diverse activities in the CYTH protein family.
J.Biol.Chem., 297:100820-100820, 2021

PubMed Abstract: CYTH proteins make up a large superfamily that is conserved in all three domains of life. These enzymes have a triphosphate tunnel metalloenzyme (TTM) fold, which typically results in phosphatase functions, e.g., RNA triphosphatase, inorganic polyphosphatase, or thiamine triphosphatase. Some CYTH orthologs cyclize nucleotide triphosphates to 3',5'-cyclic nucleotides. So far, archaeal CYTH proteins have been annotated as adenylyl cyclases, although experimental evidence to support these annotations is lacking. To address this gap, we characterized a CYTH ortholog, SaTTM, from the crenarchaeote Sulfolobus acidocaldarius. Our in silico studies derived ten major subclasses within the CYTH family implying a close relationship between these archaeal CYTH enzymes and class IV adenylyl cyclases. However, initial biochemical characterization reveals inability of SaTTM to produce any cyclic nucleotides. Instead, our structural and functional analyses show a classical TTM behavior, i.e., triphosphatase activity, where pyrophosphate causes product inhibition. The Ca-inhibited Michaelis complex indicates a two-metal-ion reaction mechanism analogous to other TTMs. Cocrystal structures of SaTTM further reveal conformational dynamics in SaTTM that suggest feedback inhibition in TTMs due to tunnel closure in the product state. These structural insights combined with further sequence similarity network-based in silico analyses provide a firm molecular basis for distinguishing CYTH orthologs with phosphatase activities from class IV adenylyl cyclases.

PubMed: 34029589
DOI: 10.1016/j.jbc.2021.100820

実験手法

X-RAY DIFFRACTION (2.3 Å)