5OHX

Structure of active cystathionine B-synthase from Apis mellifera

Summary for 5OHX

• Entry DOI: 10.2210/pdb5ohx/pdb
• Descriptor: Cystathionine beta-synthase, PROTOPORPHYRIN IX CONTAINING FE, PYRIDOXAL-5'-PHOSPHATE (3 entities in total)
• Functional Keywords: cbs, transsulfuration, hydrogen sulfide, h2s, homocystinuria, s-adenosylmethionine, adomet, lyase
• Biological source: Apis mellifera (Honey bee); More
• Total number of polymer chains: 2
• Total formula weight: 114298.59

Authors

Gimenez-Mascarell, P.,Majtan, T.,Oyenarte, I.,Ereno-Orbea, J.,Majtan, J.,Kraus, J.P.,Klaudiny, J.,Martinez-Cruz, L.A. (deposition date: 2017-07-18, release date: 2018-01-03, Last modification date: 2024-01-17)

Primary citation

Gimenez-Mascarell, P.,Majtan, T.,Oyenarte, I.,Ereno-Orbea, J.,Majtan, J.,Klaudiny, J.,Kraus, J.P.,Martinez-Cruz, L.A.
Crystal structure of cystathionine beta-synthase from honeybee Apis mellifera.
J. Struct. Biol., 202:82-93, 2018

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.

PubMed: 29275181
DOI: 10.1016/j.jsb.2017.12.008

Experimental method

X-RAY DIFFRACTION (3.2 Å)