Conformational transformations of SAHase

S-adenosyl-L-homocysteine hydrolase (SAHase) decomposes SAH to adenosine and homocysteine, and this way helps to drive forward SAM (S-adenosyl-methionine) dependent methylation reactions, which accumulate SAH as their inhibitory byproduct. Although the SAHase reaction looks like a simple hydrolysis, its mechanism is quite complicated as it involves red-ox steps. This is why SAHase requires NAD+ as cofactor. The enzyme is a homotetramer of four subunits, each comprised of the N-terminal substrate-binding domain (blue), the cofactor-binding domain (red) and a small dimerization domain (yellow). (The tetramer can be viewed as a dimer of intimate dimers.) During the reaction cycle, the two main domains assume a closed conformation when a substrate molecule (here represented by a molecule of adenosine) is bound, and then open up to release the reaction products. During those 'breathing' motions, a molecular gate element (a His-Phe tandem) opens and shuts an active site access channel leading right to the center of the catalytic apparatus.

Tomek's results were published in Acta Crystallographica (Acta Cryst. D71, 2422-2432, 2015) and in IUCr Journal (IUCrJ 4, 271-282, 2017).

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Last update: March 26, 2018 (MJ)