Crystal structure of cystathionine β-synthase from honeybee Apis mellifera

<div>Cystathionine β-synthase (CBS), the key enzyme in the transsulfuration pathway, links methionine metabolism</div><div>to the biosynthesis of cellular redox controlling molecules. CBS catalyzes the pyridoxal-5′-phosphate-dependent</div><div>condensation of serine and homocysteine to form cystathionine, which is subsequently converted into cysteine.</div><div>Besides maintaining cellular sulfur amino acid homeostasis, CBS also catalyzes multiple hydrogen sulfide-generating</div><div>reactions using cysteine and homocysteine as substrates. In mammals, CBS is activated by S-adenosylmethionine</div><div>(AdoMet), where it can adopt two different conformations (basal and activated), but exists as a</div><div>unique highly active species in fruit fly Drosophila melanogaster. Here we present the crystal structure of CBS from</div><div>honeybey Apis mellifera, which shows a constitutively active dimeric species and let explain why the enzyme is</div><div>not allosterically regulated by AdoMet. In addition, comparison of available CBS structures unveils a substrateinduced</div><div>closure of the catalytic cavity, which in humans is affected by the AdoMet-dependent regulation and</div><div>likely impaired by the homocystinuria causing mutation T191M.</div>