5ohx

Publication Abstract from PubMed

Cystathionine beta-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.

Crystal structure of cystathionine beta-synthase from honeybee Apis mellifera.,Gimenez-Mascarell P, Majtan T, Oyenarte I, Ereno-Orbea J, Majtan J, Klaudiny J, Kraus JP, Martinez-Cruz LA J Struct Biol. 2017 Dec 21. pii: S1047-8477(17)30231-9. doi:, 10.1016/j.jsb.2017.12.008. PMID:29275181^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.