The enzyme cystathionine β-synthase (CBS) catalyzes the condensation of serine and homocysteine to produce cystathionine, an important intermediate in the biosynthesis of cysteine. Deficiency of CBS activity results in toxic levels of homocysteine and is the most common cause of homocystinuria, a disease whose symptoms include dislocated eye lenses, skeletal and vascular problems, and mental retardation.  Although the catalytic chemistry of CBS is performed by its coenzyme pyridoxal 5'-phosphate (PLP), heme is essential for activity in human CBS. Heme is also found in Drosophila CBS. However, the CBS enzymes of lower organisms (e.g. yeast) do not need heme at all. Why, then, has nature included a heme in the CBS in the course of evolution? A number of hypotheses have been put out base on previous studies, including both structural and regulatory roles for the heme. However, there is still no concensus on what the heme does in CBS. In collaboration with Professor Jan Kraus ( (University of Colorado, Denver), we are currently probing the enzyme and the heme with a variety of spectroscopic and biochemical methods, such as electronic absorption and magnetic circular dichroism (MCD), and resonance Raman spectroscopies, site-directed mutagenesis, radiochemical enzyme assays, tandem affinity purification (TAP) in an attempt to unlock the mystery of the heme in this enzyme.
CBS crystal structure
The crystal structure of human CBS Δ414-551 reveals a dimer with heme and PLP cofactors (boxed, right). The regions of the enzyme which we think stabilize the heme are shaded in red. The CBS heme is six-coordinate with the amino acids histidine and cysteine serving as axial ligands (upper left). This type of heme coordination is very rare and may be responsible for the unique properties of the CBS heme.