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 2

Structure of CBS p.P49L. X-ray crystallographic structure of CBS p.P49L solved at 2.80 Å resolution (PDB entry 5MMS). (a) Cartoon representation of the protein dimer, each monomer being represented in a different color. Pyridoxal 5′-phosphate (PLP) and heme moieties shown in stick representation. (b) Structure superposition of CBS p.P49L (PDB entry 5MMS) and truncated WT CBS (PDB entry 1JBQ), both colored in grey except for most relevant regions and residues, where CBS p.P49L is colored in red and CBS WT in blue; zoom in on the PLP and heme moieties, highlighting the proline-to-leucine substitution, as well as the R266 residue and α-helix 8 proposed to mediate communication between the heme and the PLP active site. Figure generated with PyMOL 1.8.2 (The PyMOL Molecular Graphics System, Version 1.8 Schrödinger, LLC).

(a)

(b)