Structure of human cystathionine beta-synthase: a unique pyridoxal 5 '-phosphate-dependent heme protein

Cystathionine beta -synthase (CBS) is a unique heme-containing enzyme that catalyzes a pyridoxal 5 ' -phosphate (PLP)-dependent condensation of serine and homocysteine to give cystathionine. Deficiency of CBS leads to homocys tinuria, an inherited disease of sulfur metabolism characterized by increas ed levels of the toxic metabolite homocysteine. Here we present the X-ray c rystal structure of a truncated form of the enzyme. CBS shares the same fol d with O-acetylserine sulfhydrylase but it contains an additional N-termina l heme binding site. This heme binding motif together with a spatially adja cent oxidoreductase active site motif could explain the regulation of its e nzyme activity by redox changes.