Download MendeleyCrystal Structures of Cystathionine beta-Synthase from Saccharomyces cerevisiae: One Enzymatic Step at a Time.
Tu, Y., Kreinbring, C.A., Hill, M., Liu, C., Petsko, G.A., McCune, C.D., Berkowitz, D.B., Liu, D., Ringe, D.(2018) Biochemistry 57: 3134-3145
- PubMed: 29630349
- DOI: https://doi.org/10.1021/acs.biochem.8b00092
- Primary Citation of Related Structures:
6C2H, 6C2Q, 6C2Z, 6C4P - PubMed Abstract:
Cystathionine β-synthase (CBS) is a key regulator of sulfur amino acid metabolism, taking homocysteine from the methionine cycle to the biosynthesis of cysteine via the trans-sulfuration pathway. CBS is also a predominant source of H 2 S biogenesis. Roles for CBS have been reported for neuronal death pursuant to cerebral ischemia, promoting ovarian tumor growth, and maintaining drug-resistant phenotype by controlling redox behavior and regulating mitochondrial bioenergetics. The trans-sulfuration pathway is well-conserved in eukaryotes, but the analogous enzymes have different enzymatic behavior in different organisms. CBSs from the higher organisms contain a heme in an N-terminal domain. Though the presence of the heme, whose functions in CBSs have yet to be elucidated, is biochemically interesting, it hampers UV-vis absorption spectroscopy investigations of pyridoxal 5'-phosphate (PLP) species. CBS from Saccharomyces cerevisiae (yCBS) naturally lacks the heme-containing N-terminal domain, which makes it an ideal model for spectroscopic studies of the enzymological reaction catalyzed and allows structural studies of the basic yCBS catalytic core (yCBS-cc). Here we present the crystal structure of yCBS-cc, solved to 1.5 Å. Crystal structures of yCBS-cc in complex with enzymatic reaction intermediates have been captured, providing a structural basis for residues involved in catalysis. Finally, the structure of the yCBS-cc cofactor complex generated by incubation with an inhibitor shows apparent off-pathway chemistry not normally seen with CBS.
Organizational Affiliation:
Department of Biochemistry , Brandeis University , Waltham , Massachusetts 02454 , United States.
