Crystal structure of cystathionine β-synthase from honeybee Apis mellifera

J Struct Biol. 2018 Apr;202(1):82-93. doi: 10.1016/j.jsb.2017.12.008. Epub 2017 Dec 21.

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.

Keywords: CBS; Homocystinuria; Hydrogen sulfide; S-adenosylmethionine; Transsulfuration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bees
  • Crystallography, X-Ray
  • Cystathionine beta-Synthase / chemistry*
  • Cystathionine beta-Synthase / genetics
  • Cystathionine beta-Synthase / metabolism
  • Cysteine / metabolism
  • Homocysteine / metabolism
  • Humans
  • Insect Proteins / chemistry*
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Models, Molecular
  • Protein Conformation*
  • Protein Multimerization*
  • S-Adenosylmethionine / metabolism
  • Sequence Homology, Amino Acid
  • Substrate Specificity

Substances

  • Insect Proteins
  • Homocysteine
  • S-Adenosylmethionine
  • Cystathionine beta-Synthase
  • Cysteine