Crystal Structures of Cystathionine β‑Synthase
from Saccharomyces cerevisiae: One
Enzymatic Step at a Time
Version 2 2018-04-16, 12:20
Version 1 2018-04-13, 19:35
Posted on 2018-04-16 - 12:20
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 H2S 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.
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Tu, Yupeng; Kreinbring, Cheryl A.; Hill, Megan; Liu, Cynthia; Petsko, Gregory A.; McCune, Christopher D.; et al. (2018). Crystal Structures of Cystathionine β‑Synthase
from Saccharomyces cerevisiae: One
Enzymatic Step at a Time. ACS Publications. Collection. https://doi.org/10.1021/acs.biochem.8b00092
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AUTHORS (9)
YT
Yupeng Tu
CK
Cheryl A. Kreinbring
MH
Megan Hill
CL
Cynthia Liu
GP
Gregory A. Petsko
CM
Christopher D. McCune
DB
David B. Berkowitz
DL
Dali Liu
DR
Dagmar Ringe