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.