7LOW

S-adenosylmethionine synthetase

Summary for 7LOW

• Entry DOI: 10.2210/pdb7low/pdb
• Descriptor: S-adenosylmethionine synthase, PYROPHOSPHATE 2-, PHOSPHATE ION, ... (6 entities in total)
• Functional Keywords: s-adenosylmethionine synthetase, transferase
• Biological source: Escherichia coli 908573
• Total number of polymer chains: 2
• Total formula weight: 86810.28

Authors

Tan, L.L.,Jackson, C.J. (deposition date: 2021-02-10, release date: 2021-03-31, Last modification date: 2023-10-18)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.39 Å)