Oligomeric status of human cystathionine beta-synthase modulates AdoMet binding

Cystathionine beta-synthase (CBS) plays a key role in the metabolism of sulfur-
containing amino acids. CBS is a multidomain tetrameric enzyme
allosterically activated by S-adenosylmethionine (AdoMet). Recent crystallographic
analyses of engineered CBS lacking the loop made up of residues
516–525 revealed discrepancies in AdoMet binding compared to previous biophysical
studies on a full-length CBS. Here, we show that removal of the loop
516–525 functionally eliminates the high affinity sites responsible for kinetic
stabilization of the full-length enzyme and yields a dimeric AdoMet-inducible
enzyme, in which kinetic stabilization is now exerted by AdoMet binding to
the remaining low affinity sites.