7LOO

S-adenosyl methionine transferase cocrystallized with ATP

7LOO の概要

• エントリーDOI: 10.2210/pdb7loo/pdb
• 分子名称: S-adenosylmethionine synthase, PYROPHOSPHATE 2-, PHOSPHATE ION, ... (8 entities in total)
• 機能のキーワード: s-adenosyl methionine transferase, transferase
• 由来する生物種: Escherichia coli 908573
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 172377.82

構造登録者

Jackson, C.J.,Tan, L.L.,Laurino, P. (登録日: 2021-02-10, 公開日: 2021-09-15, 最終更新日: 2023-10-18)

主引用文献

Gade, M.,Tan, L.L.,Damry, A.M.,Sandhu, M.,Brock, J.S.,Delaney, A.,Villar-Briones, A.,Jackson, C.J.,Laurino, P.
Substrate Dynamics Contribute to Enzymatic Specificity in Human and Bacterial Methionine Adenosyltransferases.
Jacs Au, 1:2349-2360, 2021

PubMed Abstract: Protein conformational changes can facilitate the binding of noncognate substrates and underlying promiscuous activities. However, the contribution of substrate conformational dynamics to this process is comparatively poorly understood. Here, we analyze human (hMAT2A) and (eMAT) methionine adenosyltransferases that have identical active sites but different substrate specificity. In the promiscuous hMAT2A, noncognate substrates bind in a stable conformation to allow catalysis. In contrast, noncognate substrates sample stable productive binding modes less frequently in eMAT owing to altered mobility in the enzyme active site. Different cellular concentrations of substrates likely drove the evolutionary divergence of substrate specificity in these orthologues. The observation of catalytic promiscuity in hMAT2A led to the detection of a new human metabolite, methyl thioguanosine, that is produced at elevated levels in a cancer cell line. This work establishes that identical active sites can result in different substrate specificity owing to the effects of substrate and enzyme dynamics.

PubMed: 34977903
DOI: 10.1021/jacsau.1c00464

実験手法

X-RAY DIFFRACTION (1.95 Å)