A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme Cystathionine β-Synthase: Increased CO Reactivity as a Novel Molecular Mechanism of Pathogenicity?

Figure 4

Enhanced CO affinity of p.P49L CBS. Absorption spectra collected upon anaerobic titration of reduced CBS p.P49L (1.4–1.6 μM in heme) with CO, in the absence (a) or presence (b) of AdoMet. = 20°C. (c) Titration profiles obtained by global fit of the spectral data acquired in the absence (full circles) or presence (hollow squares) of 500 μM AdoMet. Data were best fitted according to (1), yielding = 0.05 μM (60%) and = 22.0 μM (40%) for AdoMet-free CBS p.P49L and ≤ 0.03 μM (70%) and = 2.1 μM (30%) for the AdoMet-bound enzyme. Gray lines represent titration curves for WT CBS in the absence (dotted line) and presence (dashed line) of 500 μM AdoMet.

(a)

(b)

(c)