Structural insight into the molecular mechanism of allosteric activation of human cystathionine β-synthase by S-adenosylmethionine.

ABSTRACT: Cystathionine β-synthase (CBS) is a heme-dependent and pyridoxal-5'-phosphate-dependent protein that controls the flux of sulfur from methionine to cysteine, a precursor of glutathione, taurine, and H2S. Deficiency of CBS activity causes homocystinuria, the most frequent disorder of sulfur amino acid metabolism. In contrast to CBSs from lower organisms, human CBS (hCBS) is allosterically activated by S-adenosylmethionine (AdoMet), which binds to the regulatory domain and triggers a conformational change that allows the protein to progress from the basal toward the activated state. The structural basis of the underlying molecular mechanism has remained elusive so far. Here, we present the structure of hCBS with bound AdoMet, revealing the activated conformation of the human enzyme. Binding

SUBMITTER: Ereno-Orbea J 

PROVIDER: S-EPMC4169959 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature