Crystal Structure of cystathionine β-synthase from honeybee Apis mellifera

Publication date: Available online 21 December 2017 Source:Journal of Structural Biology Author(s): Paula Giménez-Mascarell, Tomas Majtan, Iker Oyenarte, June Ereño-Orbea, Juraj Majtan, Jaroslav Klaudiny, Jan P. Kraus, Luis Alfonso Martínez-Cruz Cystathionine β-synthase (CBS), the key enzyme in the transsulfuration pathway, links methionine metabolism to the biosynthesis of cellular redox controlling molecules. CBS catalyzes the pyridoxal-5’-phosphate-dependent condensation of serine and homocysteine to form cystathionine, which is subsequently converted into cysteine. Besides maintaining cellular sulfur amino acid homeostasis, CBS also catalyzes multiple hydrogen sulfide-generating reactions using cysteine and homocysteine as substrates. In mammals, CBS is activated by S-adenosylmethionine (AdoMet), where it can adopt two different conformations (basal and activated), but exists as a unique highly active species in fruit fly Drosophila melanogaster. Here we present the crystal structure of CBS from honeybey Apis mellifera, which shows a constitutively active dimeric species and let explain why the enzyme is not allosterically regulated by AdoMet. In addition, comparison of available CBS structures unveils a substrate-induced closure of the catalytic cavity, which in humans is affected by the AdoMet-dependent regulation and likely impaired by the homocystinuria causing mutation T191M.

Source: Journal of Structural Biology - December 22, 2017 Category: Biology Source Type: research