Oligomeric status of human cystathionine beta-synthase modulates AdoMet binding

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