Structural basis for substrate activation and regulation by cystathionine beta-synthase (CBS) domains in cystathionine β-synthase

• DOI: 10.1073/pnas.1011448107
• Publication Date: 2010-11-17T03:38:46Z
• Authors: Markos Koutmos; Omer Kabil; Janet L. Smith; Ruma Banerjee
• Keywords: Tryptophan synthase; Homocystinuria

The catalytic potential for H 2 S biogenesis and homocysteine clearance converge at the active site of cystathionine β-synthase (CBS), a pyridoxal phosphate-dependent enzyme. CBS catalyzes β-replacement reactions either serine or cysteine by to give water S, respectively. In this study, high-resolution structures full-length enzyme from Drosophila in which carbanion (1.70 Å) an aminoacrylate intermediate (1.55 have been captured are reported. Electrostatic stabilization zwitterionic is afforded close positioning lysine residue that initially used Schiff base formation internal aldimine later as general base. Additional stabilizing interactions between residues intermediates observed. Furthermore, structure regulatory “energy-sensing” domains, named after protein, suggests mechanism allosteric activation -adenosylmethionine.