6C4P

Crystal Structures of Cystathionine beta-Synthase from Saccharomyces cerevisiae: the Structure of the PMP Complex

Summary for 6C4P

• Entry DOI: 10.2210/pdb6c4p/pdb
• Related: 6C2H 6C2Q 6C2Z
• Descriptor: Cystathionine beta-synthase, 4'-DEOXY-4'-AMINOPYRIDOXAL-5'-PHOSPHATE, CALCIUM ION, ... (8 entities in total)
• Functional Keywords: cbs, synthase, plp, lyase
• Biological source: Saccharomyces cerevisiae (Baker's yeast)
• Total number of polymer chains: 1
• Total formula weight: 42031.86

Authors

Kreinbring, C.A.,Tu, Y.,Liu, D.,Berkowitz, D.B.,Petsko, G.A.,Ringe, D. (deposition date: 2018-01-12, release date: 2018-04-25, Last modification date: 2023-10-04)

Primary citation

Tu, Y.,Kreinbring, C.A.,Hill, M.,Liu, C.,Petsko, G.A.,McCune, C.D.,Berkowitz, D.B.,Liu, D.,Ringe, D.
Crystal Structures of Cystathionine beta-Synthase from Saccharomyces cerevisiae: One Enzymatic Step at a Time.
Biochemistry, 57:3134-3145, 2018

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 HS 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.

PubMed: 29630349
DOI: 10.1021/acs.biochem.8b00092

Experimental method

X-RAY DIFFRACTION (2.3 Å)