Download MendeleyCrystal structure of cystathionine beta-synthase from honeybee Apis mellifera.
Gimenez-Mascarell, P., Majtan, T., Oyenarte, I., Ereno-Orbea, J., Majtan, J., Klaudiny, J., Kraus, J.P., Martinez-Cruz, L.A.(2018) J Struct Biol 202: 82-93
- PubMed: 29275181
- DOI: https://doi.org/10.1016/j.jsb.2017.12.008
- Primary Citation of Related Structures:
5OHX - PubMed Abstract:
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.
Organizational Affiliation:
Structural Biology Unit, Center for Cooperative Research in Biosciences (CIC Biogune), Technology Park of Bizkaia, 48160 Derio, Bizkaia, Spain.
