Hydrogen Sulfide Biochemistry and Interplay with Other Gaseous Mediators in Mammalian Physiology

Figure 4

Crystallographic structure of human cystathionine β-synthase (CBS). (a) Cartoon representation of the “full-length” human CBS homodimer (PDB ID: 4COO; Δ516–525; 2.0 Å resolution). Green sticks, active site PLP moiety, where H₂S production occurs. Orange sticks, regulatory heme b where CO or NO binds, resulting in enzyme inhibition. (b) Zoom-in into the catalytic (PLP) and regulatory (heme) sites. The PLP moiety is covalently attached to CBS through Lys₁₁₉ (human CBS numbering), while the b-type heme is axially coordinated by Cys₅₂ and His₆₅. Orange arrow indicates the communication between the heme and PLP sites mediated by the α-helix comprising residues Thr₂₅₇-Gly₂₅₈-Gly₂₅₉-Thr₂₆₀-Ile₂₆₁-Thr₂₆₂-Gly₂₆₃-Ile₂₆₄-Ala₂₆₅-Arg₂₆₆. (c) Structural effect of AdoMet binding. While in AdoMet-free CBS, the C-terminal domain of each monomer (C1_free and C2_free, colored in light gray) blocks the substrate entrance into the active site (green oval circle) of the adjacent monomer, AdoMet binding to the C-terminal domains leads to association of the latter in a disk-like form (C1_bound and C2_bound; PDB ID: 4PCU; Δ516–525 Glu201Ser; 3.58 Å resolution), unblocking the active site and derepressing the enzymatic activity. Figure generated with PyMol 1.8.2.0 [238].