2 research outputs found
Comparative Study of Enzyme Activity and Heme Reactivity in <i>Drosophila melanogaster</i> and <i>Homo sapiens</i> Cystathionine β‑Synthases
Cystathionine β-synthase (CBS) is the first and
rate-limiting
enzyme in the transsulfuration pathway, which is critical for the
synthesis of cysteine from methionine in eukaryotes. CBS uses coenzyme
pyridoxal 5′-phosphate (PLP) for catalysis, and <i>S</i>-adenosylmethionine regulates the activity of human CBS, but not
yeast CBS. Human and fruit fly CBS contain heme; however, the role
for heme is not clear. This paper reports biochemical and spectroscopic
characterization of CBS from fruit fly <i>Drosophila melanogaster</i> (<i>Dm</i>CBS) and the CO/NO gas binding reactions of <i>Dm</i>CBS and human CBS. Like CBS enzymes from lower organisms
(e.g., yeast), <i>Dm</i>CBS is intrinsically highly active
and is not regulated by AdoMet. The <i>Dm</i>CBS heme coordination
environment, the reactivity, and the accompanying effects on enzyme
activity are similar to those of human CBS. The <i>Dm</i>CBS heme bears histidine and cysteine axial ligands, and the enzyme
becomes inactive when the cysteine ligand is replaced. The Fe(II)
heme in <i>Dm</i>CBS is less stable than that in human CBS,
undergoing more facile reoxidation and ligand exchange. In both CBS
proteins, the overall stability of the protein is correlated with
the heme oxidation state. Human and <i>Dm</i>CBS Fe(II)
hemes react relatively slowly with CO and NO, and the rate of the
CO binding reaction is faster at low pH than at high pH. Together,
the results suggest that heme incorporation and AdoMet regulation
in CBS are not correlated, possibly providing two independent means
for regulating the enzyme