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2 L-cysteine
(2R,2'R)-3,3'-sulfanediylbis(2-aminopropanoic acid) + H2S
beta-Chloro-DL-alanine + DL-homocysteine
?
-
-
-
-
?
beta-Cyano-DL-alanine + DL-homocysteine
?
-
-
-
-
?
DL-Serine-O-sulfate + DL-homocysteine
?
-
-
-
-
?
L-allothreonine + homocysteine
? + H2O
-
-
-
?
L-cysteine
H2S + L-serine
-
-
-
?
L-Cysteine + 1-butanethiol
?
L-Cysteine + 1-mercapto-2-propanol
HOOC-CH(NH2)-CH2-S-CH2-CH(OH)-CH3 + H2S
L-Cysteine + 1-pentanethiol
?
L-Cysteine + 2-mercaptoethanol
HOOC-CH(NH2)-CH2-S-CH2-CH2OH + H2S
L-cysteine + 2-mercaptoethanol
S-hydroxyethyl-L-cysteine + H2S
L-Cysteine + cysteamine
?
L-Cysteine + dithioerythritol
?
L-Cysteine + dithiothreitol
?
L-Cysteine + DL-homocysteine
Cystathionine + H2S
L-cysteine + H2O
L-serine + H2S
A0A1J9VES8
-
-
-
?
L-cysteine + L-homocysteine
L-cystathionine + H2S
L-cysteine + L-serine
lanthionine + H2O
-
-
-
?
L-Cysteine + monothioglycerol
?
L-serine + cysteamine
L-thialysine
-
-
-
-
?
L-serine + H2O
NH3 + pyruvate
-
wild-type enzyme shows no beta-elimination reaction, beta elimination is only detectable in the following mutants: T81A, S82A, T85A, Q157A, Q157E, Q157H, Y158F
-
?
L-serine + H2S
L-cysteine
-
-
-
?
L-Serine + homocysteine
?
L-Serine + homocysteine
Cystathionine + H2O
L-Serine + HS-
Cysteine + OH-
L-serine + L-cysteine
?
-
-
-
-
?
L-serine + L-homocysteine
?
-
-
-
-
r
L-serine + L-homocysteine
cystathionine + H2O
L-serine + L-homocysteine
L-cystathionine + H2O
O-acetyl-L-serine
L-cysteine + acetate
O-acetyl-L-serine + H2O
pyruvate + acetate + NH3
O-acetyl-L-serine + H2S
L-cysteine + acetic acid
A0A1J9VES8
-
-
-
?
O-acetyl-L-serine + L-homocysteine
?
-
poor substrate for both the wild type and the N- and C-terminally truncated enzyme 71400 CBS
-
-
?
O-acetyl-L-serine + L-homocysteine
cystathionine + acetate
S-Methyl-L-cysteine + DL-homocysteine
?
-
-
-
-
?
additional information
?
-
2 L-cysteine
(2R,2'R)-3,3'-sulfanediylbis(2-aminopropanoic acid) + H2S
-
-
-
?
2 L-cysteine
(2R,2'R)-3,3'-sulfanediylbis(2-aminopropanoic acid) + H2S
-
-
-
?
cysteine + ?
H2S + ?
-
-
-
-
?
cysteine + ?
H2S + ?
-
-
-
-
?
L-Cysteine + 1-butanethiol
?
-
-
-
-
?
L-Cysteine + 1-butanethiol
?
-
-
-
-
?
L-Cysteine + 1-mercapto-2-propanol
HOOC-CH(NH2)-CH2-S-CH2-CH(OH)-CH3 + H2S
-
-
-
-
?
L-Cysteine + 1-mercapto-2-propanol
HOOC-CH(NH2)-CH2-S-CH2-CH(OH)-CH3 + H2S
-
-
-
-
?
L-Cysteine + 1-mercapto-2-propanol
HOOC-CH(NH2)-CH2-S-CH2-CH(OH)-CH3 + H2S
-
-
-
-
?
L-Cysteine + 1-mercapto-2-propanol
HOOC-CH(NH2)-CH2-S-CH2-CH(OH)-CH3 + H2S
-
activated L-serine sulfhydrase
-
?
L-Cysteine + 1-pentanethiol
?
-
-
-
-
?
L-Cysteine + 1-pentanethiol
?
-
-
-
-
?
L-Cysteine + 2-mercaptoethanol
HOOC-CH(NH2)-CH2-S-CH2-CH2OH + H2S
-
-
-
-
?
L-Cysteine + 2-mercaptoethanol
HOOC-CH(NH2)-CH2-S-CH2-CH2OH + H2S
-
-
-
?
L-Cysteine + 2-mercaptoethanol
HOOC-CH(NH2)-CH2-S-CH2-CH2OH + H2S
-
-
-
-
?
L-Cysteine + 2-mercaptoethanol
HOOC-CH(NH2)-CH2-S-CH2-CH2OH + H2S
-
-
-
?
L-Cysteine + 2-mercaptoethanol
HOOC-CH(NH2)-CH2-S-CH2-CH2OH + H2S
-
-
-
-
?
L-Cysteine + 2-mercaptoethanol
HOOC-CH(NH2)-CH2-S-CH2-CH2OH + H2S
Steinernema bibionis
-
-
-
-
?
L-Cysteine + 2-mercaptoethanol
HOOC-CH(NH2)-CH2-S-CH2-CH2OH + H2S
-
-
-
-
?
L-cysteine + 2-mercaptoethanol
S-hydroxyethyl-L-cysteine + H2S
-
-
-
-
?
L-cysteine + 2-mercaptoethanol
S-hydroxyethyl-L-cysteine + H2S
-
-
?
L-Cysteine + cysteamine
?
-
-
-
-
?
L-Cysteine + cysteamine
?
-
-
-
-
?
L-Cysteine + dithioerythritol
?
-
-
-
-
?
L-Cysteine + dithioerythritol
?
-
-
-
-
?
L-Cysteine + dithiothreitol
?
-
-
-
-
?
L-Cysteine + dithiothreitol
?
-
-
-
-
?
L-Cysteine + DL-homocysteine
Cystathionine + H2S
-
-
-
-
?
L-Cysteine + DL-homocysteine
Cystathionine + H2S
-
full-length enzyme and truncated enzyme form lacking the C-terminal regulatory domain
-
-
?
L-Cysteine + DL-homocysteine
Cystathionine + H2S
-
-
-
-
?
L-Cysteine + DL-homocysteine
Cystathionine + H2S
-
-
-
?
L-Cysteine + DL-homocysteine
Cystathionine + H2S
-
-
-
?
L-Cysteine + DL-homocysteine
Cystathionine + H2S
-
-
-
?
L-Cysteine + DL-homocysteine
Cystathionine + H2S
-
-
-
-
?
L-cysteine + L-homocysteine
L-cystathionine + H2S
A0A1J9VES8
-
-
-
?
L-cysteine + L-homocysteine
L-cystathionine + H2S
-
-
-
-
r
L-cysteine + L-homocysteine
L-cystathionine + H2S
-
-
-
?
L-cysteine + L-homocysteine
L-cystathionine + H2S
-
-
-
?
L-cysteine + L-homocysteine
L-cystathionine + H2S
-
-
-
?
L-cysteine + L-homocysteine
L-cystathionine + H2S
-
-
-
-
r
L-Cysteine + monothioglycerol
?
-
-
-
-
?
L-Cysteine + monothioglycerol
?
-
-
-
-
?
L-Cysteine + monothioglycerol
?
-
-
-
-
?
L-Serine + homocysteine
?
-
-
-
-
?
L-Serine + homocysteine
?
-
-
-
-
?
L-Serine + homocysteine
?
-
synthesis of cystathionine
-
-
?
L-Serine + homocysteine
?
-
-
-
-
?
L-Serine + homocysteine
?
-
-
-
-
?
L-Serine + homocysteine
?
-
irreversible step in transsulfuration pathway
-
-
?
L-Serine + homocysteine
?
-
reduced activity of EC 4.2.1.22 in patients with homocystinuria due to mutations in the CBS gene
-
-
?
L-Serine + homocysteine
?
-
-
-
-
?
L-Serine + homocysteine
?
-
-
-
-
?
L-Serine + homocysteine
?
-
-
-
-
?
L-Serine + homocysteine
?
-
initial step in transsulfuration forming cysteine. Homocysteine is a relatively toxic amino acid, which levels have to be kept low
-
-
?
L-Serine + homocysteine
?
-
synthesis of cystathionine
-
-
?
L-Serine + homocysteine
?
-
-
-
-
?
L-Serine + homocysteine
?
-
reverse trans-sulfuration pathway
-
-
?
L-Serine + homocysteine
?
Steinernema bibionis
-
-
-
-
?
L-Serine + homocysteine
?
-
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
ir
-
?
L-Serine + homocysteine
Cystathionine + H2O
beta-replacement reaction
-
?
L-Serine + homocysteine
Cystathionine + H2O
catalyzes a beta-replacement reaction in which an electronegative substituent in the beta-position of the amino acid substrate is replaced by a nucleophile, binding of L-serine as the external aldimine is faster than formation of the aminoacrylate intermediate, the rate-limiting step is the reaction of aminoacrylate with L-homocysteine to form L-cystathione, rate of the forward reaction is 38fold greater than the reverse reaction
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
hydroxylgroup of serine is replaced by the thiol of homocysteine
-
r
L-Serine + homocysteine
Cystathionine + H2O
-
in the forward direction an external aldimine of serine and an aminoacrylate intermediate are formed, the aminoacrylate binds to homocysteine and converts to cystathione, in the reverse reaction cystathione binds to the enzyme and is rapidly converted to the aminoacrylate without accumulation of the external aldimine
-
r
L-Serine + homocysteine
Cystathionine + H2O
Steinernema bibionis
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
Steinernema bibionis
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
-
-
-
r
L-Serine + HS-
Cysteine + OH-
-
-
-
?
L-Serine + HS-
Cysteine + OH-
-
-
-
?
L-Serine + HS-
Cysteine + OH-
-
-
-
?
L-Serine + HS-
Cysteine + OH-
-
-
-
?
L-Serine + HS-
Cysteine + OH-
-
-
-
?
L-Serine + HS-
Cysteine + OH-
-
-
-
?
L-Serine + HS-
Cysteine + OH-
-
-
-
?
L-Serine + HS-
Cysteine + OH-
Steinernema bibionis
-
-
-
?
L-Serine + HS-
Cysteine + OH-
-
-
-
?
L-serine + L-homocysteine
cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
cystathionine + H2O
-
-
-
?
L-serine + L-homocysteine
cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
cystathionine + H2O
the enzyme participates in the process of oocyte maturation
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
electrostatic stabilization of the zwitterionic carbanion intermediate is afforded by the close positioning of an active site lysine residue that is initially used for Schiff base formation in the internal aldimine and later as a general base, and additional stabilizing interactions between active site residues and the catalytic intermediates
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
696253, 697295, 698182, 698850, 701064, 704664, 714179, 714912, 715808, 715809, 728933, 728945, 730143, 730146, 730755 -
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
ir
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
?
O-acetyl-L-serine
L-cysteine + acetate
A0A1J9VES8
-
-
-
?
O-acetyl-L-serine
L-cysteine + acetate
-
-
-
?
O-acetyl-L-serine
L-cysteine + acetate
-
-
-
?
O-acetyl-L-serine + H2O
pyruvate + acetate + NH3
-
-
-
?
O-acetyl-L-serine + H2O
pyruvate + acetate + NH3
-
-
-
?
O-acetyl-L-serine + L-homocysteine
cystathionine + acetate
-
-
-
?
O-acetyl-L-serine + L-homocysteine
cystathionine + acetate
-
-
-
?
additional information
?
-
O-acetylserine sulfhydrylase isozyme A, OASSAp, EC 2.5.1.65, exhibits both O-acetylserine sulfhydrylase and cystathionine beta-synthase activities
-
-
?
additional information
?
-
A0A1J9VES8
no substrate: L-serine
-
-
?
additional information
?
-
-
no substrate: L-serine
-
-
?
additional information
?
-
-
key enzyme involved in intracellular metabolism of homocysteine
-
?
additional information
?
-
-
elevated total plasma homocysteine is an independent risk factor in the development of vascular disease in humans. Elevating cystathionine beta-synthase level is an effective method to lower plasma homocysteine levels
-
-
?
additional information
?
-
-
the enzyme may have additional in vivo functions beyond its role as a homocysteine metabolizing enzyme
-
-
?
additional information
?
-
-
the overexpression of cystathionine beta-synthase may cause the developmental abnormality in cognition in Down's syndrome children and may lead to Alzheimer type of disease in Down's syndrom adults
-
-
?
additional information
?
-
-
the cystathionine beta-synthase variant c.844_845ins68 protects against CNS demyelination in X-linked adrenoleukodystrophy
-
-
?
additional information
?
-
-
the oxidation of CBS by dioxygen appears to proceed directly from the ferrous to the ferric state, presumably via an outer sphere electron transfer reaction
-
-
?
additional information
?
-
-
CBS also catalyze H2S production in vitro
-
-
?
additional information
?
-
-
the enzyme performs L-cysteine sythesis from L-serine
-
-
?
additional information
?
-
-
the enzyme performs L-cysteine sythesis from L-serine
-
-
?
additional information
?
-
cysteine is able to partially compete with serine on CBS, thus leading to generation of appreciable amounts of H2S. The leading H2S-producing reaction is condensation of cysteine with homocysteine, while cysteine desulfuration plays a dominant role when cysteine is more abundant than serine and homocysteine is limited. The serine-to-cysteine ratio is the main determinant of CBS H2S productivity. Abundance of cysteine over serine, for example, in blood plasma, allows for up to 43% of CBS activity being responsible for H2S production, while excess of serine typical for intracellular levels effectively limited such activity to less than 1.5%. CBS also produces lanthionine from serine and cysteine
-
-
?
additional information
?
-
-
first step in transsulfuration pathway
-
?
additional information
?
-
-
cystathionine beta-synthase is a key enzyme for homocysteine metabolism, it is associated with the generation and/or differentiation of the radial glia/astrocyte linage cells in the developing central nervous system
-
-
?
additional information
?
-
-
hyperhomocysteinaemia is a metabolic disorder associated with the development of premature atherosclerosis. Cystathionine beta-synthase activity is significantly decreased in mice with a plasma homocysteine value greater than 0.015 mg
-
-
?
additional information
?
-
-
role for CBS as a mediator in interactions between oocyte and granulosa cells
-
-
?
additional information
?
-
-
CBS also catalyze H2S production in vitro
-
-
?
additional information
?
-
-
no L-serine sulfhydrase activity
-
-
?
additional information
?
-
-
cystathionine-beta-synthase domains in the ATP-binding component of OpuC are required for transporter function
-
-
?
additional information
?
-
-
plasma albumin cysteinylation is regulated by cystathionine beta-synthase
-
-
?
additional information
?
-
-
CBS also catalyze H2S production in vitro
-
-
?
additional information
?
-
-
no substrate: L-threonine
-
?
additional information
?
-
-
no substrates: D-, L-allo- and D-allo-cystathionine
-
?
additional information
?
-
-
cystathionine beta-synthase also catalyze H2S production. The most efficient route for H2S generation by cystathionine beta-synthase is the beta-replacement of the cysteine thiol with homocysteine. In this reaction, cystathionine beta-synthase first reacts with cysteine to release H2S and forms an aminoacrylate intermediate. Homocysteine binds to the E 3 aminoacrylate intermediate with a bimolecular rate constant of 142 mM/s and rapidly condenses to form the enzyme-bound external aldimine of cystathionine. The reactions could be partially rate limited by release of the products, cystathionine and H2S
-
-
?
additional information
?
-
-
key enzyme in the trans-sulfuration pathway. Cystathionine beta-synthase may be an oxidative defense enzyme in the eye tissue, in particular in the segments of the eye where constant environmental oxidative stress is imposed
-
-
?
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1.72 - 24
2-mercaptoethanol
68
DL-homocysteine
-
cosubstrate L-Ser
0.083 - 0.9
L-cystathionine
additional information
additional information
-
pre-steady-state kinetic analysis of enzyme-monitored turnover during cystathionine beta-synthase-catalyzed H2S generation, overview
-
1.72
2-mercaptoethanol
-
-
5.58
2-mercaptoethanol
-
-
24
2-mercaptoethanol
-
cosubstrate L-Cys
5.6
cysteamine
-
pH 8.0, 37°C, UV assay
6.6
cysteamine
-
pH 8.0, 37°C, Mudd assay
4.7
H2S
cosubstrate L-serine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
5.02
H2S
cosubstrate L-serine, pH 7.4, 37°C
0.05
homocysteine
-
S466L mutant, 37°C, absence of S-adenosyl-L-methionine
0.08
homocysteine
-
wild-type enzyme, 37°C, presence of S-adenosyl-L-methionine
0.1
homocysteine
-
I435T mutant, 37°C, absence of S-adenosyl-L-methionine
0.17
homocysteine
-
wild-type enzyme, 37°C, absence of S-adenosyl-L-methionine
0.2
homocysteine
-
I435T mutant, 37°C, presence of S-adenosyl-L-methionine
0.8
homocysteine
-
enzyme composed of MW 48000 subunits
1.1
homocysteine
-
absence of S-adenosyl-L-methionine
1.2
homocysteine
-
37°C, L-serine pre-treatment
2
homocysteine
-
37°C, pH 8.6, mutant enzyme I278T
2.3
homocysteine
-
37°C, homocysteine pre-treatment
3.41
homocysteine
-
enzyme form beta
3.98
homocysteine
-
enzyme form alpha
4.8
homocysteine
-
absence of S-adenosyl-L-methionine, recombinant enzyme
5
homocysteine
-
presence of S-adenosyl-L-methionine, recombinant enzyme
5
homocysteine
-
pH 6.8, 37°C, full length enzyme after L-serine pre-treatment
7.17
homocysteine
-
37°C, pH 8.6, mutant enzyme R266K
7.17
homocysteine
-
37°C, pH 8.6, wild-type enzyme
9.7
homocysteine
-
pH 6.8, 37°C, deltaC143 mutant after L-serine pre-treatment
15
homocysteine
-
pH 6.8, 37°C, full length enzyme after homocysteine pre-treatment
18
homocysteine
-
cosubstrate L-Ser
25
homocysteine
-
enzyme composed of MW 68000 subunits
67
homocysteine
-
pH 6.8, 37°C, deltaC143 mutant after homocysteine pre-treatment
0.13
L-Cys
-
-
36
L-Cys
-
cosubstrate 2-mercaptoethanol
0.083
L-cystathionine
-
pH 8.6, 37°C, reverse reaction
0.13
L-cystathionine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
0.14
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), wild-type
0.9
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), mutant S289A
2
L-cysteine
-
wild-type
3
L-cysteine
formation of L-cystathionine, mutant A70S, pH 7.5, 37°C
3.59
L-cysteine
-
37°C, pH 8.6, mutant enzyme I278T
4.3
L-cysteine
-
37°C, pH 8.6, mutant enzyme R266K
4.4
L-cysteine
-
mutant R266K
5.4
L-cysteine
-
mutant H67A
5.5
L-cysteine
-
mutant R266K
5.9
L-cysteine
formation of L-cystathionine, wild-type, pH 7.5, 37°C
6.11
L-cysteine
-
37°C, pH 8.6, wild-type enzyme
8.11
L-cysteine
cosubstrate H2O, pH 7.4, 37°C
8.41
L-cysteine
cosubstrate H2O, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
8.9
L-cysteine
formation of (2R,2'R)-3,3'-sulfanediylbis(2-aminopropanoic acid), wild-type, pH 7.5, 37°C
13.41
L-cysteine
cosubstrate L-homocysteine, pH 7.4, 37°C
15.92
L-cysteine
cosubstrate L-homocysteine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
37
L-cysteine
formation of (2R,2'R)-3,3'-sulfanediylbis(2-aminopropanoic acid), mutant E223G, pH 7.5, 37°C
37
L-cysteine
formation of L-cystathionine, mutant E223G, pH 7.5, 37°C
0.16
L-homocysteine
-
mutant S289A
0.21
L-homocysteine
-
wild-type
0.29
L-homocysteine
wild-type, 37°C, pH not specified in the publication
0.3
L-homocysteine
-
pH 8.6, 37°C
0.31
L-homocysteine
mutant K523Sfs?18, 37°C, pH not specified in the publication
0.32
L-homocysteine
mutant S500L, 37°C, pH not specified in the publication
0.32
L-homocysteine
A0A1J9VES8
wild-type, production of H2S, pH 8.2, 37°C
0.35
L-homocysteine
mutant V449G, 37°C, pH not specified in the publication
0.4
L-homocysteine
formation of L-cystathionine, mutant E223G, pH 7.5, 37°C
0.4
L-homocysteine
mutant D444N, 37°C, pH not specified in the publication
0.43
L-homocysteine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
0.47
L-homocysteine
mutant L540Q, 37°C, pH not specified in the publication
0.54
L-homocysteine
formation of L-cystathionine, wild-type, pH 7.5, 37°C
0.69
L-homocysteine
mutant P427L, 37°C, pH not specified in the publication
1
L-homocysteine
-
37°C, pH 8.0, wild-type enzyme, with S-adenosyl-L-methionine
1
L-homocysteine
synthesis of L-cystathionine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
1.04
L-homocysteine
-
37°C, pH 8.0, wild-type enzyme, without S-adenosyl-L-methionine
1.04
L-homocysteine
synthesis of L-cystathionine, pH 7.4, 37°C
1.1
L-homocysteine
-
mutant enzyme S466L, in the presence of 0.25 mM S-adenosyl-L-methionine
1.3
L-homocysteine
-
mutant R266K
1.51
L-homocysteine
A0A1J9VES8
mutant E220R, pH 8.2, 37°C
1.6
L-homocysteine
-
mutant R266K
2.5
L-homocysteine
-
wild type enzyme, in the presence of 0.25 mM S-adenosyl-L-methionine
2.73
L-homocysteine
A0A1J9VES8
wild-type, pH 8.2, 37°C
3.4
L-homocysteine
-
mutant H67A
3.59
L-homocysteine
A0A1J9VES8
mutant A72S, pH 8.2, 37°C
3.7
L-homocysteine
-
pH 8.0, 37°C
4.31
L-homocysteine
cosubstrate L-cysteine, pH 7.4, 37°C
4.48
L-homocysteine
cosubstrate L-cysteine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
5
L-homocysteine
-
wild-type
20
L-homocysteine
formation of L-cystathionine, mutant A70S, pH 7.5, 37°C
0.91
L-Ser
-
-
2
L-Ser
-
no influence of S-adenosyl-L-methionine, recombinant enzyme
3.1
L-Ser
-
absence of S-adenosyl-L-methionine
6
L-Ser
-
value is reduced 8fold by S-adenosyl-L-methionine
0.7
L-serine
-
wild-type
0.77
L-serine
-
mutant enzyme S466L, in the presence of 0.25 mM S-adenosyl-L-methionine
0.78
L-serine
-
wild type enzyme, in the presence of 0.25 mM S-adenosyl-L-methionine
1.2
L-serine
-
pH 8.6, 37°C
1.2
L-serine
-
pH 8.0, 37°C, reaction with cysteamine, continous UV assay
1.27
L-serine
cosubstrate H2S, pH 7.4, 37°C
1.32
L-serine
cosubstrate H2S, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
1.41
L-serine
-
37°C, pH 8.0, wild-type enzyme, without -adenosyl-L-methionine
1.41
L-serine
-
37°C, pH 8.6, mutant enzyme I278T
1.41
L-serine
synthesis of L-cystathionine, pH 7.4, 37°C
1.74
L-serine
-
37°C, pH 8.6, wild-type enzyme
1.9
L-serine
mutant L540Q, 37°C, pH not specified in the publication
2
L-serine
-
pH 6.8, 37°C, full length enzyme after L-serine pre-treatment
2
L-serine
mutant P427L, 37°C, pH not specified in the publication
2.1
L-serine
mutant S500L, 37°C, pH not specified in the publication
2.13
L-serine
-
37°C, pH 8.0, wild-type enzyme, with S-adenosyl-L-methionine
2.13
L-serine
synthesis of L-cystathionine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
2.2
L-serine
-
pH 8.0, 37°C, reaction with cysteamine, Mudd assay
2.7
L-serine
mutant V449G, 37°C, pH not specified in the publication
2.76
L-serine
-
37°C, pH 8.6, mutant enzyme R266K
2.9
L-serine
mutant D444N, 37°C, pH not specified in the publication
3.5
L-serine
-
37°C, homocysteine pre-treatment
3.6
L-serine
-
wild-type enzyme, 37°C, presence of S-adenosyl-L-methionine
3.6
L-serine
wild-type, 37°C, pH not specified in the publication
3.7
L-serine
mutant K523Sfs?18, 37°C, pH not specified in the publication
4.2
L-serine
-
I435T mutant, 37°C, absence of S-adenosyl-L-methionine
4.5
L-serine
-
I435T mutant, 37°C, presence of S-adenosyl-L-methionine
4.9
L-serine
-
37°C, L-serine pre-treatment
4.9
L-serine
-
wild-type enzyme, 37°C, absence of S-adenosyl-L-methionine
4.9
L-serine
-
pH 8.0, 37°C, reaction with L-homocysteine
5
L-serine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
5.5
L-serine
-
pH 6.8, 37°C, full length enzyme after homocysteine pre-treatment
7.2
L-serine
-
S466L mutant, 37°C, absence of S-adenosyl-L-methionine
14
L-serine
-
pH 6.8, 37°C, deltaC143 mutant after homocysteine pre-treatment
18
L-serine
-
pH 6.8, 37°C, deltaC143 mutant after L-serine pre-treatment
27.1
L-serine
-
mutant S289A
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0.0045 - 6.08
L-cystathionine
0.024 - 26.78
L-homocysteine
additional information
additional information
-
the kcat for the generation of H2S by cystathionine beta-synthase of 55/s at 37°C, via the condensation of cysteine and homocysteine is 18fold faster than that for the beta-elimination and rehydration to form serine of 3/s-
-
0.35
H2S
cosubstrate L-serine, pH 7.4, 37°C
0.78
H2S
cosubstrate L-serine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
5.9
homocysteine
-
I435T mutant, 37°C, absence of S-adenosyl-L-methionine
6.2
homocysteine
-
wild-type enzyme, 37°C, absence of S-adenosyl-L-methionine
15.5
homocysteine
-
S466L mutant, 37°C, absence of S-adenosyl-L-methionine
32.1
homocysteine
-
I435T mutant, 37°C, presence of S-adenosyl-L-methionine
34
homocysteine
-
wild-type enzyme, 37°C, presence of S-adenosyl-L-methionine
0.0045
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), mutant S289A
0.083
L-cystathionine
-
S82A mutant, pH 8.6, 37°C
0.133
L-cystathionine
-
T85A mutant, pH 8.6, 37°C
0.418
L-cystathionine
-
Y158F mutant, pH 8.6, 37°C
0.56
L-cystathionine
-
pH 8.6, 37°C
0.56
L-cystathionine
-
wild-type enzyme, pH 8.6, 37°C
1.03
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), wild-type
6.08
L-cystathionine
-
pH 8.6, 37°C
6.08
L-cystathionine
-
wild-type enzyme, pH 8.6, 37°C
0.022
L-cysteine
formation of (2R,2'R)-3,3'-sulfanediylbis(2-aminopropanoic acid), mutant E223G, pH 7.5, 37°C
0.04
L-cysteine
-
37°C, pH 8.6, mutant enzyme I278T
0.6
L-cysteine
formation of L-cystathionine, mutant E223G, pH 7.5, 37°C
1.06
L-cysteine
cosubstrate H2O, pH 7.4, 37°C
1.1
L-cysteine
formation of (2R,2'R)-3,3'-sulfanediylbis(2-aminopropanoic acid), wild-type, pH 7.5, 37°C
1.41
L-cysteine
cosubstrate H2O, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
1.95
L-cysteine
-
37°C, pH 8.6, mutant enzyme R266K
2
L-cysteine
formation of L-cystathionine, mutant A70S, pH 7.5, 37°C
3.13
L-cysteine
-
37°C, pH 8.6, wild-type enzyme
4.39
L-cysteine
-
37°C, pH 8.6, wild-type enzyme
7.09
L-cysteine
cosubstrate L-homocysteine, pH 7.4, 37°C
7.6
L-cysteine
formation of L-cystathionine, wild-type, pH 7.5, 37°C
31.34
L-cysteine
cosubstrate L-homocysteine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
0.024
L-homocysteine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
0.031 - 0.51
L-homocysteine
-
37°C, pH 8.6, wild-type enzyme
0.04 - 1.97
L-homocysteine
-
37°C, pH 8.6, mutant enzyme R266K
0.09
L-homocysteine
-
37°C, pH 8.6, mutant enzyme I278T
0.85
L-homocysteine
-
cosubstrate: L-serine, mutant S289A
3.3
L-homocysteine
-
37°C, pH 8.0, wild-type enzyme, without S-adenosyl-L-methionine
3.38
L-homocysteine
A0A1J9VES8
wild-type, production of H2S, pH 8.2, 37°C
4.66
L-homocysteine
-
37°C, pH 8.0, wild-type enzyme, without S-adenosyl-L-methionine
4.66
L-homocysteine
cosubstrate L-serine, pH 7.4, 37°C
5.74
L-homocysteine
A0A1J9VES8
mutant E220R, pH 8.2, 37°C
7.93
L-homocysteine
-
37°C, pH 8.6, wild-type enzyme
8.17
L-homocysteine
cosubstrate L-cysteine, pH 7.4, 37°C
8.39
L-homocysteine
A0A1J9VES8
wild-type, pH 8.2, 37°C
9.06
L-homocysteine
-
37°C, pH 8.6, mutant enzyme R266K
10.91
L-homocysteine
A0A1J9VES8
mutant A72S, pH 8.2, 37°C
12.7
L-homocysteine
-
37°C, pH 8.0, wild-type enzyme, with S-adenosyl-L-methionine
12.7
L-homocysteine
cosubstrate L-serine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
17
L-homocysteine
-
cosubstrate: L-serine, wild-type
21.5
L-homocysteine
-
pH 8.6, 37°C
26.78
L-homocysteine
cosubstrate L-cysteine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
0.052 - 2.1
L-serine
-
37°C, pH 8.6, wild-type enzyme
0.082
L-serine
-
Q157H mutant, pH 8.6, 37°C
0.15
L-serine
-
37°C, pH 8.6, mutant enzyme I278T
0.39
L-serine
cosubstrate H2S, pH 7.4, 37°C
0.45
L-serine
-
T81A mutant, pH 8.6, 37°C
0.52
L-serine
-
37°C, pH 8.0, wild-type enzyme, with S-adenosyl-L-methionine
0.62
L-serine
cosubstrate H2S, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
0.85
L-serine
-
cosubstrate: L-homocysteine, mutant S289A
1.3
L-serine
-
pH 8.0, 37°C, reaction with cysteamine, continous UV assay
1.67
L-serine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
2.5
L-serine
-
pH 8.0, 37°C, reaction with cysteamine, Mudd assay
2.9
L-serine
-
37°C, pH 8.6, mutant enzyme R266K
3.67
L-serine
-
37°C, pH 8.0, wild-type enzyme, without S-adenosyl-L-methionine
3.67
L-serine
cosubstrate L-homocysteine, pH 7.4, 37°C
5.3
L-serine
-
S82A mutant, pH 8.6, 37°C
5.4
L-serine
-
wild-type enzyme, 37°C, absence of S-adenosyl-L-methionine
5.9
L-serine
-
I435T mutant, 37°C, absence of S-adenosyl-L-methionine
7.5
L-serine
-
pH 8.0, 37°C, reaction with L-homocysteine
8.2
L-serine
-
Y158F mutant, pH 8.6, 37°C
10.19
L-serine
-
37°C, pH 8.6, wild-type enzyme
13.2
L-serine
-
T85A mutant, pH 8.6, 37°C
14.01
L-serine
-
37°C, pH 8.0, wild-type enzyme, with S-adenosyl-L-methionine
14.01
L-serine
cosubstrate L-homocysteine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
14.6
L-serine
-
S466L mutant, 37°C, absence of S-adenosyl-L-methionine
14.7
L-serine
-
37°C, L-serine pre-treatment
15.8
L-serine
-
I435T mutant, 37°C, presence of S-adenosyl-L-methionine
16.8
L-serine
-
37°C, homocysteine pre-treatment
17
L-serine
-
cosubstrate: L-homocysteine, wild-type
19
L-serine
-
pH 6.8, 37°C, deltaC143 mutant after L-serine pre-treatment
19.7
L-serine
-
wild-type enzyme, 37°C, presence of S-adenosyl-L-methionine
21
L-serine
-
pH 6.8, 37°C, full length enzyme after L-serine pre-treatment
21.5
L-serine
-
wild-type enzyme, pH 8.6, 37°C
39
L-serine
-
pH 6.8, 37°C, full length enzyme after homocysteine pre-treatment
45
L-serine
-
pH 6.8, 37°C, deltaC143 mutant after homocysteine pre-treatment
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evolution
-
cystathionine beta-synthase belongs to the fold II family of pyridoxal 5'-phosphate enzymes
malfunction
-
hemizygous (+/-) CBS knockout mice are analysed: Significantly higher plasma total homocysteine concentrations occurr in the CBS (+/-) mice than in wild-type cohorts. Female mice of both genotypes have significantly higher plasma total homocysteine concentrations and lower relative CBS mRNA levels than did male mice. During vitamin B6 deficiency, plasma total homocysteine concentrations are significantly elevated. CBS (+/-) mice have a lower plasma cholesterol concentration, and during a taurine- and cysteine-deficient diet, CBS mRNA levels in CBS (+/-) mice are reduced only 13%
malfunction
-
the effects of endogenous elevation of homocysteine on the retina using the cystathionine beta-synthase mutant mouse is determined. Increased retinal homocysteine alters inner and outer retinal layers in cbs homozygous mice and older cbs heterozygous mice, and it primarily affects the cells of the ganglion cell layer in younger heterozygous mice. Elevated retinal homocysteine alters expression of genes involved in endoplasmic reticular stress, N-methyl-D-aspartate (NMDA) receptor activation, cell cycle, and apoptosis
malfunction
-
CBS deficiency due to missense mutations in the CBS gene is the most common cause of inherited homocystinuria, a treatable multisystemic disease affecting to various extent vasculature, connective tissues, and central nervous system
malfunction
-
cystathionine beta-synthase deficiency is a well-known genetic disease affecting the first step in the conversion of homocysteine to cysteine and ultimately to inorganic sulfur. The disease occurs in a mild and a severe form, phenotypes, overview. Cystathionine beta-synthase activities in wild-type individuals, and in hetero-, and homozygote cystathionine beta-synthase mutants, overview
malfunction
misfolding of mutant enzymes may play an important role in the pathogenesis of cystathionine beta-synthase deficiency, identification of mutant variants in patients with homocystinuria due to CBS deficiency and phenotypes, the topology of mutations predicts in part the behavior of mutant CBS, pathogenic mechanism in CBS deficiency, molecular dynamics simulations, overview
malfunction
-
depletion of cystathionine beta synthase induces premature senescence in human endothelial cells, induces mild mitochondrial dysfunction and increases the sensitivity of endothelial cells to homocysteine, a known inducer of endothelial cell senescence and an established risk factor for vascular disease
metabolism
-
involved in homocystein metabolism
metabolism
-
CBS is a key enzyme in the trans-sulfuration pathway and catalyzes the condensation of serine with homocysteine to produce cystathionine
metabolism
CBS is involved in the cysteine pathway of bacteria and plants, overview
metabolism
CBS is involved in the cysteine pathway of bacteria and plants, overview
metabolism
-
cystathionine beta-synthase catalyzes the first step in the transsulfuration pathway in mammals, i.e. the condensation of serine and homocysteine to produce cystathionine and water
metabolism
-
cystathionine beta-synthase is a pivotal enzyme in the metabolism of homocysteine, and is a pyridoxal 5'-phosphate-dependent enzyme that also contains heme as a second cofactor
metabolism
-
cystathionine beta-synthase is a pyridoxal 5'-phosphate-dependent enzyme, which catalyzes the first step of the transsulfuration pathway, namely, the condensation of serine with homocysteine to cystathionine
metabolism
cystathionine beta-synthase is involved in the cysteine pathway of bacteria and plants, overview
metabolism
binding of S-adenosylhomocysteine and sinefungin lead to stabilization of the regulatory domains without activation of CBS. Binding of these two ligands also affects the enzyme proteolysis
physiological function
-
CBS activity may contribute to butyrate-stimulated H2S production in WiDr cells
physiological function
-
CBS activity partially regulates endogenous H2S in mice. It contributes significantly to endogenous H2S production in mice, adenovirus-mediated overexpression of CBS in the liver significantly increases circulating levels of H2S, whereas CBS deficiency results in reduced levels. irculating H2S levels are increased by pharmacological activation of CBS in vivo; i.e. in the presence of the endogenous activator
physiological function
-
regulation mechanisms, overview
physiological function
-
Cystathionine beta synthase (CBS) is the main contributor to the production of hydrogen sulfide (H2S) in the brain. The CBS/H2S pathway plays an important role in the protection of learning and memory functions in the brain at the level of the hippocampus
physiological function
-
cystathionine beta-synthase contributes to advanced ovarian cancer progression and drug resistance. The enzyme also regulates bioenergetics of ovarian cancer cells by regulating mitochondrial reactive oxygen species production, oxygen consumption and ATP generation
physiological function
-
enzyme overexpression extends lifespan of human endothelial cells
physiological function
-
CBS silencing attenuates the expression of number of key enzymes involved in lipid synthesis, i.e. FASN and ACC1. CBS abrogates lipid uptake in ovarian cancer cells. Gene silencing of CBS or lipogenic transcription factors SREBPs abrogates cellular migration and invasion in ovarian cancer. CBS represses SREBP1 and SREBP2 at the transcription levels by modulating the transcription factor Sp1. In orthotopic tumor models, CBS or SREBP silencing results in reduced tumor cells proliferation, blood vessels formation and lipid content
physiological function
-
comparison of human, fruit fly and yeast enzymes. The fruit fly CBS and yeast CBS are not regulated by the allosteric activator of human CBS, S-adenosyl-L-methionine. The heme-containing Drosophila melanogaster CBS and human CBS show increased thermal stability and retention of the enzyme's catalytic activity
physiological function
-
comparison of human, fruit fly and yeast enzymes. Truncation of human CBS and yeast CBS, i.e. deletion of the regulatory domains, results in enzyme activation and formation of dimers compared to native tetramers The fruit fly CBS and yeast CBS are not regulated by the allosteric activator of human CBS, S-adenosyl-L-methionine. compared to the yeast CBS, the heme-containing Drosophila melanogaster CBS and human CBS show increased thermal stability and retention of the enzyme's catalytic activity
physiological function
-
comparison of human, fruit fly and yeast enzymes. Truncation of human CBS and yeast CBS, i.e. deletion of the regulatory domains, results in enzyme activation and formation of dimers compared to native tetramers. Only the human enzyme is regulated by S-adenosylmethionine. The heme-containing Drosophila melanogaster CBS and human CBS show increased thermal stability and retention of the enzyme's catalytic activity
physiological function
-
cystathionine beta-synthase reprograms mitochondrial morphogenesis in ovarian cancer cells by selectively regulating the stability of mitofusin MFN2. Clinically, high expression of both CBS and MFN2 implicates poor overall survival of ovarian cancer patients, and a significant association between CBS andMFN2 expression exists in individual patients in the same data set. The silencing of CBS by siRNA or its inhibition of creates oxidative stress that activates JNK. Activated JNK phosphorylates MFN2 to recruit homologous to the E6-AP carboxyl terminus' domain-containing ubiquitin E3 ligase for its degradation via the ubiquitin-proteasome system. In CBS-silenced orthotopic xenograft tumor tissues,MFN2 but notMFN1 is selectively downregulated
physiological function
deletion mutants of conserved domain protein/cyclin M Mg2+ transporter CNNM2, lacking the CBS domains, are unable to promote Mg2+ efflux. The CBS domains of CNNM2 bind to ATP in a Mg2+-dependent manner
physiological function
-
isoform Cbsb is responsible for anterior-posterior axis development, and Cbsa function is redundant. Cbsb loss of function fish embryos show shortened and bent axis, along with less H2S and more homocysteine
physiological function
Leishmania braziliensis promastigotes and amastigotes overexpressing cysteine synthase and cystathionine beta-synthase show enhanced ability to resist oxidative stress compared to that of nontransfected cells, resulting in a phenotype far more resistant to treatment with the pentavalent form of antimony in vitro
physiological function
-
the central domain of CBS contains a 272CXXC275 motif which exists in oxidized and reduced states. The activity of reduced CBS is 2-3fold greater than that of the oxidized enzyme, and substitution of either cysteine in CXXC motif leads to a loss of redox sensitivity. The Cys272-Cys275 disulfide bond in CBS has a midpoint potential of -314 mV at pH 7.4. Stressing HEK-293 cells with dithiothreitol results in more reduced enzyme and a concomitant increase in H2S production in live HEK293 cells
physiological function
-
the loss of CBS function in endothelial cells leads to a significant down-regulation of cellular hydrogen sulfide by 50% and of glutathione by 40%. Silencing CBS in endothelial cells compromises phenotypic and signaling responses to the vascular endothelial growth factor
additional information
-
CBS is a modular enzyme, cross-talk between the catalytic core and the regulatory domain in cystathionine beta-synthase: study by differential covalent labeling and computational modeling, overview
additional information
-
increased immunoreactivity is evident in liver homogenates from mice treated with adenovirus carrying human CBS compared to mice treated with the Ad-lacZ virus
additional information
-
increased immunoreactivity is evident in liver homogenates from mice treated with adenovirus carrying human CBS compared to mice treated with the Ad-lacZ virus. Overexpression of hCBS reduces homocysteine levels significantly by 5.3fold compared to Ad-lacZ treated mice
additional information
structural basis for substrate activation and regulation by cystathionine beta-synthase domains in cystathionine beta-synthase, allosteric regulation via the CBS domains, mechanism, overview
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A72S
A0A1J9VES8
mutant produces more H2S than wild-type
E220R
A0A1J9VES8
not able to release H2S
A331V
-
mutation effects can be suppressed in a yeast assay by the deletion of the regulatory domain of the protein
C15S
-
mutagenesis does not affect catalysis or S-adenosyl-L-methionine activation but significantly reduces aggregation of the purified enzyme in vitro
C272A
2fold lower heme content, 2fold lower specific activity, 2fold higher activity in the presence of S-adenosyl-L-methionine
C274S
2fold lower heme content, 2fold lower specific activity, 2fold higher activity in the presence of S-adenosyl-L-methionine
C431S
-
mutagenesis results in a constitutively activated form of CBS that can not be further activated by either S-adenosyl-L-methionine or thermal activation
C52A
-
reduced heme content, pyridoxal phosphate content comparable to wild-type enzyme, low catalytic activity
C52S
-
reduced heme content, pyridoxal phosphate content comparable to wild-type enzyme, low catalytic activity
D198V
pathogenic mutation, no impact on specific activity and response to AdoMet
D234N
the mutation is associated with Venezuelan homocystinuria responsive to vitamin B6. The mutant shows 43% activity compared to the wild type enzyme
D376N
-
mutant is not rescuable by any of the chemical chaperones
DELAT143
-
truncated human CBS lacking 143 amino acids at the C-terminus is purified from a recombinant expression system and is used for vibrational coherence spectroscopy
DELTAC
-
studies are carried out using a truncated protein lacking the C-terminal domain. kcat increases by a factor of 4 and the responsiveness to S-adenosyl-L-methionine is lost. The C-terminal domain is involved in the aggregation of the full-length protein, which exists as a mixture of tetramer and higher oligomers, while the 45 kDa truncated form lacking the C-terminal domain is a dimer
DELTAC143
a truncated human CBS lacking 143 amino acids at the C-terminus is used to study the inactivation of cystathionine beta-synthase by peroxynitrite
E201S
mutation leads to permanent activation of enzyme
G116R
-
mutation in dimer interface of patients with homocystinurea
G259S
-
active site mutation in patients with homocystinurea
H67A
-
mutant is comparable to wild-type, specific activity and Km values for L-Ser, L-homocysteine comparable to wild-type
I152M
-
the mutation is associated with homocystinuria
I278T/T424N
-
mutant enzyme is inactive, although transgenic mouse line that expresses I278T/T424N possess the ability to rescue the neonatal lethality associated with homozygosity for the Cbs- allele
I437T
mutation results in loss of S-adenosyl-L-methionine-dependent activation but exhibits basal activity that is comparable to that of wild-type enzyme expressed under the same conditions. Purified recombinant I435T shows a two to 3fold higher basal activity compared to wild-type enzyme but is unresponsive to the allosteric activator S-adenosyl-L-methionine
K523Sfs?18
enzymatic function of the variants is not impaired, increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
L539S
-
site-directed mutagenesis, inactive mutant, the mutant shows altered activity compared to the wild-type enzyme
L540Q
enzymatic function of the variants is not impaired, increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
P427L
enzymatic function of the variants is not impaired. Mutant lacks activation by S-adenosyl-L-methionine, but binds it at low level and shows an increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
P427L/S500L
-
the mutant is almost not activated by S-adenosyl-L-methionine
P78R/K102N
-
KM for L-serine is about 2fold higher than wild-type value. Mutant enzyme is insensitive to allosteric regulation and unresponsive to S-adenosyl-L-methionine
P88S
-
mutation in dimer interface of patients with homocystinurea
Q222X
-
mutagenesis studies reveal that Gln-222 is involved in interactions with substrates
Q526K
-
mutant is not rescuable by any of the chemical chaperones
R125W
-
the mutation is associated with homocystinuria
R224A
the mutation decreases CBS activity by approximately 50%
R224H
-
mutation in the connecting loop between the N- and C-terminal domain between beta-strand 7 and alpha-helix 6, patients respond to vitamin B6 treatment
R266G
-
patient mutation , mutant protein shows instability and extensive degradation during thrombin treatment. A GST-R266G fusion protein does not exhibit any detectable activity unlike the GST-tagged wild-type CBS
R266X
-
mutagenesis studies reveal that Arg-266 is important to sense structural changes in heme-binding site
R491C
-
the mutation is associated with homocystinuria
R51A
the mutation decreases CBS activity by approximately 50%
R58W
-
mutation in the heme binding site of patients with homocystinurea, reduced ability to bind heme
S352N
-
patients with this mutation are not vitamin B6 responsive
S500L
about 71% of wild-type activity. Mutant lacks activation by S-adenosyl-L-methionine, but binds it at low level and shows an increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
T223X
-
mutagenesis studies reveal that Tyr-223 is involved in interactions with substrates
T257M
-
active site mutation in patients with homocystinurea
T262M
-
expression of human mutant CBS proteins in Saccharomyces cerevisiae reveals that the disease causing mutation severely inhibits enzyme activity and cannot support growth of yeast on cysteine-free media. The osmolyte chemical chaperones glycerol, trimethylamine-N-oxide, dimethylsulfoxide, proline or sorbitol, when added to yeast media, allows growth on cysteine-free media and causes increased enzyme activity from I278T mutant protein. The increase in enzyme activity is associated with stabilization of the tetramer form of the enzyme. This effect is not specific to yeast, as addition of the chaperone glycerol results in increased I278T activity when the enzyme is produced either in Escherichia coli or in a coupled in vitro transcription/translation reaction. No stimulation of specific activity is observed when chaperones are added directly to purified I278T indicating that the presence of chemical chaperones is required during translation
T262R
-
site-directed mutagenesis, inactive mutant
T434N
-
the mutation is associated with homocystinuria
T87N
the mutation is associated with Venezuelan homocystinuria nonresponsive to vitamin B6. The mutant shows 3.5% activity compared to the wild type enzyme
V354M
-
patients with this mutation are not vitamin B6 responsive
V371M
-
the mutation is associated with homocystinuria
V449G
enzymatic function of the variants is not impaired, increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
A70S
residue at the substrate binding pocket, important for the H2S-generating activity
E223G
residue at the substrate binding pocket, important for the H2S-generating activity
A70S
-
residue at the substrate binding pocket, important for the H2S-generating activity
-
E223G
-
residue at the substrate binding pocket, important for the H2S-generating activity
-
C272A
-
spectroscopic properties similar to wild-type enzyme
C275S
-
spectroscopic properties similar to wild-type enzyme
T568I
substitution of amino acid residue in the CBS domains of CNNM2, abrogates Mg2+ efflux and binding of ATP
C162S
-
activity can be enhanced by sodium nitroprusside
C367S
-
activity can be enhanced by sodium nitroprusside
C476S
-
activity can be enhanced by sodium nitroprusside
C49S
-
activity can be enhanced by sodium nitroprusside
D249A
-
a series of 8 site-directed mutants is constructed, and their order of impact on the ability of ytCBS to catalyze the beta-replacement reaction is G247S asymptotically equal to K112Q bigger than K112L asymptotically equal to K112R bigger than Y248F bigger D249A asymptotically equal to H138F bigger than E136A
E136A
-
a series of 8 site-directed mutants is constructed, and their order of impact on the ability of ytCBS to catalyze the beta-replacement reaction is G247S asymptotically equal to K112Q bigger than K112L asymptotically equal to K112R bigger than Y248F bigger D249A asymptotically equal to H138F bigger than E136A
G247A
-
undetectable beta-replacement activity
H138F
-
a series of 8 site-directed mutants is constructed, and their order of impact on the ability of ytCBS to catalyze the beta-replacement reaction is G247S asymptotically equal to K112Q bigger than K112L asymptotically equal to K112R bigger than Y248F bigger D249A asymptotically equal to H138F bigger than E136A. Km (L-homocysteine) increased by 8fold
K112L
-
a series of 8 site-directed mutants is constructed, and their order of impact on the ability of ytCBS to catalyze the beta-replacement reaction is G247S asymptotically equal to K112Q bigger than K112L asymptotically equal to K112R bigger than Y248F bigger D249A asymptotically equal to H138F bigger than E136A. Km (L-Ser) increased by 50fold, Km (L-homocysteine) increased by 2fold
K112Q
-
a series of 8 site-directed mutants is constructed, and their order of impact on the ability of ytCBS to catalyze the beta-replacement reaction is G247S asymptotically equal to K112Q bigger than K112L asymptotically equal to K112R bigger than Y248F bigger D249A asymptotically equal to H138F bigger than E136A
K112R
-
a series of 8 site-directed mutants is constructed, and their order of impact on the ability of ytCBS to catalyze the beta-replacement reaction is G247S asymptotically equal to K112Q bigger than K112L asymptotically equal to K112R bigger than Y248F bigger D249A asymptotically equal to H138F bigger than E136A. Km (L-Ser) increased by 90fold, Km (L-homocysteine) increased by 4fold
Q157A
-
no detectable beta-replacement activity, catalyzes a competing beta-elimination reaction, in which L-Ser is hydrolyzed to NH3 and pyruvate
Q157E
-
no detectable beta-replacement activity, catalyzes a competing beta-elimination reaction, in which L-Ser is hydrolyzed to NH3 and pyruvate
Q157H
-
enzyme suffers suicide inhibition via a mechanism in which the released aminoacrylate intermediate covalently attacks the internal aldimine of the enzyme, catalyzes a competing beta-elimination reaction, in which L-Ser is hydrolyzed to NH3 and pyruvate
S289A
-
kcat/Km (L-serine) is reduced by 800fold compared to wild-type. Km (L-homocysteine) equal to wild-type, Km (L-serine) increased compared to wild-type. The reverse-reaction (L-cystathionine hydrolysis) shows a 1400fold reduction of kcat/Km (L-cystathionine) for mutant S289A which is dominated by a 230fold decrease in kcat. Residue S289 is essential in maintaining the properties and orientation of the pyridine ring of the pyridoxal 5'-phosphate cofactor. The reduction in activity of mutant S289A suggests that yeast CBS catalyzes the alpha, beta-elimination of L-Ser via an E1cB mechanism
S289D
-
mutant shows no beta-replacement activity. Fluorescence energy transfer between tryptophan residue(s) of the enzyme and the pyridoxal 5'-phosphate cofactor, observed in the wild-type enzyme and diminished in the S289A mutant, is absent in S289D
S82A
-
catalyzes a competing beta-elimination reaction, in which L-Ser is hydrolyzed to NH3 and pyruvate
T81A
-
catalyzes a competing beta-elimination reaction, in which L-Ser is hydrolyzed to NH3 and pyruvate
T85A
-
catalyzes a competing beta-elimination reaction, in which L-Ser is hydrolyzed to NH3 and pyruvate
Y158F
-
3fold decreased beta-replacement activity, enzyme suffers suicide inhibition via a mechanism in which the released aminoacrylate intermediate covalently attacks the internal aldimine of the enzyme, catalyzes a competing beta-elimination reaction, in which L-Ser is hydrolyzed to NH3 and pyruvate
Y248F
-
a series of 8 site-directed mutants is constructed, and their order of impact on the ability of ytCBS to catalyze the beta-replacement reaction is G247S asymptotically equal to K112Q bigger than K112L asymptotically equal to K112R bigger than Y248F bigger D249A asymptotically equal to H138F bigger than E136A. Km (L-homocysteine) increased by 18fold
A114V
-
mutation in dimer interface of patients with homocystinurea, variable amounts of residual activity
A114V
-
mutation in the heme binding site of patients with homocystinurea
A114V
-
the presence of a chemical chaperone (ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide) in the medium during expression increases the mutant CBS activity in Escherichia coli crude extracts at least equal to wild-type, mutants show significant change in the level of active CBS tetramers in the presence of chaperones, mutant responds to a S-adenosyl-L-methionine stimulation or heating to 53°C with an increased activity
A114V
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
A114V
-
site-directed mutagenesis, mutation at the dimer-dimer interface, the mutant shows a decrease in specific activity compared to the wild-type enzyme
A114V
-
the mutant in the active core has slightly increased urea unfolding with decreased stability and shows 76.9% activity compared to the wild type enzyme
A226T
-
mutation in the connecting loop between the N- and C-terminal domain between beta-strand 7 and alpha-helix 6, patients respond to vitamin B6 treatment
A226T
-
mutant exhibits slight rescue with trimethylamine N-oxide and proline, but not glycerol, DMSO, or sorbitol
C165Y
-
the mutation is associated with homocystinuria
C165Y
-
site-directed mutagenesis, the mutant shows an increase in specific activity compared to the wild-type enzyme
D444N
-
high level of enzyme activity
D444N
-
mutant is unresponsive to physiological S-adenosyl-L-methionine concentrations, but can be activated in the presence of supraphysiological concentrations
D444N
basal activity of the recombinant D444N mutant is 1.5fold higher than that of wild-type enzyme under similar conditions but 1.3fold lower than wild-type enzyme in the presence of S-adenosyl-L-methionine. D444N mutant retains the ability to bind AdoMet albeit with reduced affinity
D444N
-
the mutation is associated with homocystinuria
D444N
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
D444N
-
site-directed mutagenesis, the mutant shows altered activity compared to the wild-type enzyme
D444N
-
the mutant shows 97% activity compared to the wild type enzyme when expressed in Escherichia coli
D444N
-
the mutant with substitution in the C-terminal regulatory domain shows increased global stability with decreased flexibility and shows 163.8% activity compared to the wild type enzyme
D444N
about 95% of wild-type activity, increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
D444N
pathogenic mutation, increased basal activity
E144K
-
site-directed mutagenesis, inactive mutant
E144K
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
E176K
-
mutation in dimer interface of patients with homocystinurea
E176K
-
mutation in dimer interface of patients with homocystinurea, patients do not respond to vitamin B6 treatment, mutant forms high molecular wight aggregates devoid of heme after expression in Escherichia coli
E176K
-
the presence of a chemical chaperone (ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide) in the medium during expression increases the mutant CBS activity in Escherichia coli crude extracts at least equal to wild-type, mutants show significant change in the level of active CBS tetramers in the presence of chaperones, mutant does not respond to a S-adenosyl-L-methionine stimulation or heating to 53°C with an increased activity
E176K
-
site-directed mutagenesis, the mutant shows a decrease in specific activity compared to the wild-type enzyme
E302K
-
site-directed mutagenesis, the mutant shows altered activity compared to the wild-type enzyme
E302K
-
the mutant in the active core has slightly increased urea unfolding with decreased stability and shows 95.4% activity compared to the wild type enzyme
G148R
-
active site mutation in patients with homocystinurea
G148R
-
site-directed mutagenesis, inactive mutant
G305R
-
active site mutation in patients with homocystinurea
G305R
-
site-directed mutagenesis, inactive mutant
G307S
-
active site mutation in patients with homocystinurea
G307S
-
site-directed mutagenesis, inactive mutant
G307S
-
mutant is not rescuable by any of the chemical chaperones
G307S
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
G307S
-
the mutant in the active core has slightly increased urea unfolding with decreased stability and shows 0.2% activity compared to the wild type enzyme
H65R
-
reduced heme and pyridoxal phosphate content, low catalytic activity
H65R
-
site-directed mutagenesis, inactive mutant
H65R
-
the mutant in the active core has extensive urea unfolding with decreased stability and shows 3.9% activity compared to the wild type enzyme
I278T
-
located in the middle of beta-strand 9 and the beta-sheet of the C-terminal domain, effects of this mutation can be suppressed when expressed in yeast by certain point mutations in the regulatory domain or by complete deletion of the C-terminal region
I278T
-
site-directed mutagenesis, inactive mutant
I278T
-
mutant enzyme is inactive, although transgenic mouse line that expresses I278T possess the ability to rescue the neonatal lethality associated with homozygosity for the Cbs- allele
I278T
-
1-5% of the specific activity of the wild-type enzyme. Decreased activity is due to reduced turnover rate and not substrate binding. Mutant enzyme does not have altered affinity for 5'-pyridoxal phosphate. KM-value for pyridoxal 5'-phosphate is 1.4fold lower than wild-type value. KM-value for L-serine is 1.2fold lower than wild-type value. KM-value for L-homocysteine is 3.6fold higher than wild-type value. KM-value for L-cysteine is 1.7 fold lower than wild-type value
I278T
-
expression of human mutant CBS proteins in Saccharomyces cerevisiae reveals that the disease causing mutation severely inhibits enzyme activity and cannot support growth of yeast on cysteine-free media. The osmolyte chemical chaperones glycerol, trimethylamine-N-oxide, dimethylsulfoxide, proline or sorbitol, when added to yeast media, allows growth on cysteine-free media and causes increased enzyme activity from I278T mutant protein. The increase in enzyme activity is associated with stabilization of the tetramer form of the enzyme. This effect is not specific to yeast, as addition of the chaperone glycerol results in increased I278T activity when the enzyme is produced either in Escherichia coli or in a coupled in vitro transcription/translation reaction. No stimulation of specific activity is observed when chaperones are added directly to purified I278T indicating that the presence of chemical chaperones is required during translation
I278T
-
the mutation is associated with homocystinuria
I278T
-
I278T mutant is expressed in Saccharomyces cerevisiae. By manipulation of the cellular chaperone environment the enzymatic function is resuced. Ethanol treatment induces Hsp70 and causes increased activity and steady-state levels of I278T. Exposure of I278T yeast to a 45°C heat shock for 3 h results in a 312% increase in steady-state CBS and a 511% increase in CBS activity. Hsp70 and Hsp26 bind specifically to I278T. Deletion of the SSA2 gene, which encodes a cytoplasmic isoform of Hsp70, eliminates the ability of ethanol to restore function, indicating that Hsp70 plays a positive role in proper I278T folding. In contrast, deletion of HSP26 results in increased I278T protein and activity, whereas overexpression of Hsp26 results in reduced I278T protein. The Hsp26-I278T complex is degraded via a ubiquitin/proteosome-dependent mechanism
I278T
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
I278T
-
the mutant in the active core has extensive urea unfolding with decreased stability and shows 0.3% activity compared to the wild type enzyme
I278T
-
the mutant shows 0.7% activity compared to the wild type enzyme when expressed in Escherichia coli
I435T
-
inducible by S-adenosyl-L-methionine, but less responsive than wild-type enzyme to physiologically relevant concentrations
I435T
-
the presence of a chemical chaperone (ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide) in the medium during expression increases the mutant CBS activity in Escherichia coli crude extracts at least equal to wild-type, mutants show significant change in the level of active CBS tetramers in the presence of chaperones, mutant responds to a S-adenosyl-L-methionine stimulation or heating to 53°C with an increased activity
I435T
-
site-directed mutagenesis, the mutant shows an increase in specific activity compared to the wild-type enzyme
K102N
-
KM for L-serine is about 2fold higher than wild-type value. KM for L-homocysteine is 2fold higher than wild-type value
K102N
-
site-directed mutagenesis, the mutant shows a decrease in specific activity compared to the wild-type enzyme
N228K
-
active site mutation in patients with homocystinurea
N228K
-
site-directed mutagenesis, inactive mutant
N228S
-
active site mutation in patients with homocystinurea
N228S
-
mutant is not rescuable by any of the chemical chaperones
P422L
-
the presence of a chemical chaperone (ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide) in the medium during expression increases the mutant CBS activity in Escherichia coli crude extracts at least equal to wild-type, mutants show significant change in the level of active CBS tetramers in the presence of chaperones, mutant responds to a S-adenosyl-L-methionine stimulation or heating to 53°C with an increased activity
P422L
-
site-directed mutagenesis, mutation in the regulatory domain, the mutant shows an increase in specific activity compared to the wild-type enzyme
P49L
-
site-directed mutagenesis
P49L
-
the presence of a chemical chaperone (ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide) in the medium during expression increases the mutant CBS activity in Escherichia coli crude extracts at least equal to wild-type, mutants show significant change in the level of active CBS tetramers in the presence of chaperones, mutant responds to a S-adenosyl-L-methionine stimulation or heating to 53°C with an increased activity
P49L
-
the mutant shows 39% activity compared to the wild type enzyme when expressed in Escherichia coli
P78R
-
mutation in dimer interface of patients with homocystinurea
P78R
-
KM for L-serine is about 4fold higher than wild-type value. KM for L-homocysteine is comparable to wild-type value
P78R
-
the presence of a chemical chaperone (ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide) in the medium during expression increases the mutant CBS activity in Escherichia coli crude extracts at least equal to wild-type, mutants show significant change in the level of active CBS tetramers in the presence of chaperones, mutant responds to a S-adenosyl-L-methionine stimulation or heating to 53°C with an increased activity
P78R
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site-directed mutagenesis, mutation at the dimer-dimer interface
R125Q
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the presence of a chemical chaperone (ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide) in the medium during expression increases the mutant CBS activity in Escherichia coli crude extracts at least equal to wild-type, mutants show significant change in the level of active CBS tetramers in the presence of chaperones, mutant does not respond to a S-adenosyl-L-methionine stimulation or heating to 53°C with an increased activity
R125Q
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
R125Q
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site-directed mutagenesis, the mutant shows a decrease in specific activity compared to the wild-type enzyme
R125Q
pathogenic mutation, no impact on specific activity and response to AdoMet
R266K
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site-directed mutagenesis, inactive mutant
R266K
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30-100% of the specific activity of the wild-type enzyme. Decreased activity is due to reduced turnover rate and not substrate binding. Reduced affinity for 5'-pyridoxal phosphate compared to the wild type enzyme. KM-value for pyridoxal 5'-phosphate is 2.9fold higher than wild-type value. KM-value for L-serine is 1.6fold lower than wild-type value. KM-value for L-homocysteine is identical to wild-type value. KM-value for L-cysteine is 1.4 fold lower than wild-type value
R266K
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mutant is moderately pyridoxal 5'-phosphate responsive, Km value for serine is slightly elevated compared to wild-type CBS, Km value for homocysteine slightly lower compared to wild-type
R266K
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
R266M
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enzyme is inactivated, pyridoxal 5'-phosphate is displaced by breaking the salt bridge between Cys52 and Arg266
R266M
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R266M mutant shows a significantly lower basal activity, Km value for serine is slightly elevated compared to wild-type CBS, Km value for homocysteine slightly lower compared to wild-type, R266M mutant shows dramatic differences in the ferrous state. The electrostatic interaction between C52 and R266 is critical for stabilizing the ferrous heme and its disruption leads to the facile formation of a 424 nm (C-424) absorbing ferrous species, which is inactive, compared to the active 449 nm ferrous species for wild-type CBS. Resonance Raman studies on the R266M mutant reveal that the kinetics of C52 rebinding after Fe-CO photolysis are comparable to that of wild-type CBS
R336C
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mutation causes a mild disease type
R336C
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mutation in dimer interface of patients with homocystinurea
R336H
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mutation causes a mild disease type
R336H
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mutation in dimer interface of patients with homocystinurea
R336H
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the mutant shows 0.43% activity compared to the wild type enzyme when expressed in Escherichia coli
R369C
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the mutation is associated with homocystinuria
R369C
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site-directed mutagenesis, the mutant shows a decrease in specific activity compared to the wild-type enzyme
R369C
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the mutant in the active core has extensive urea unfolding with decreased stability and shows 1.8% activity compared to the wild type enzyme
R439Q
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site-directed mutagenesis, the mutant shows altered activity compared to the wild-type enzyme
R439Q
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the mutant with substitution in the C-terminal regulatory domain shows increased global stability with decreased flexibility and shows 117.2% activity compared to the wild type enzyme
S466L
enzyme is constitutively activated, does bind S-adenosyl-L-methionine, but is not activated by it
S466L
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not inducible by S-adenosyl-L-methionine
S466L
mutant exhibits a higher basal activity than wild-type enzyme but cannot be further activated by the allosteric effecto S-adenosyl-L-methionine
S466L
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the mutation causes hyperhomocysteinemia by affecting both the steady state level of CBS protein and by reducing the efficiency of the enzyme in vivo, S466L is enzymatically active, forms tetramers, and lacks S-adenosyl-L-methionine inducibility
S466L
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the presence of a chemical chaperone (ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide) in the medium during expression increases the mutant CBS activity in Escherichia coli crude extracts at least equal to wild-type, mutants show significant change in the level of active CBS tetramers in the presence of chaperones, mutant responds to a S-adenosyl-L-methionine stimulation or heating to 53°C with an increased activity
S466L
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site-directed mutagenesis, mutation in the regulatory domain, the mutant shows an increase in specific activity compared to the wild-type enzyme
S466L
pathogenic mutation, increased basal activity
T191M
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site-directed mutagenesis, inactive mutant
T191M
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
T191M
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the mutant in the active core has extensive urea unfolding with decreased stability and shows 0.3% activity compared to the wild type enzyme
T353M
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mutation effects can be suppressed in a yeast assay by the deletion of the regulatory domain of the protein, patients with this mutation are not vitamin B6 responsive
T353M
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expression of human mutant CBS proteins in Saccharomyces cerevisiae reveals that the disease causing mutation severely inhibits enzyme activity and cannot support growth of yeast on cysteine-free media. The osmolyte chemical chaperones glycerol, trimethylamine-N-oxide, dimethylsulfoxide, proline or sorbitol, when added to yeast media, allows growth on cysteine-free media and causes increased enzyme activity from I278T mutant protein. The increase in enzyme activity is associated with stabilization of the tetramer form of the enzyme. This effect is not specific to yeast, as addition of the chaperone glycerol results in increased I278T activity when the enzyme is produced either in Escherichia coli or in a coupled in vitro transcription/translation reaction. No stimulation of specific activity is observed when chaperones are added directly to purified I278T indicating that the presence of chemical chaperones is required during translation
V180A
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mutation in dimer interface of patients with homocystinurea
V180A
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the mutation is associated with homocystinuria
V180A
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site-directed mutagenesis, mutation at the dimer-dimer interface, the mutant shows a decrease in specific activity compared to the wild-type enzyme
W409_G453del
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site-directed mutagenesis, inactive mutant
W409_G453del
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
additional information
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C-terminal regulatory domain deletion leads to formation of highly active dimeric enzyme
additional information
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CBSdeltaC143, truncated catalytic core in which the C-terminal 143 amino acid residues are deleted, higher Km for the substrates
additional information
deletion mutant CBSdeltaN43/deltaC143 lacking C-terminal and N-terminal amino acids
additional information
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deletion mutant CBSdeltaN43/deltaC143 lacking C-terminal and N-terminal amino acids
additional information
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deletion of 70 N-terminal residues results in a heme-free protein retaining 20% activity, additional deletion of 151 C-terminal residues results in an inactive enzyme, deletion of 8 C-terminal residues results in increased enzyme activity and abolishes any further activation by S-adenosyl-L-methionine
additional information
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c.833T4C transition (p.I278 T) in the cystathionine beta synthase gene represents the most common cause of pyridoxine-responsive homocystinuria in Western Eurasians. The frequency of the pathogenic c.833C allele, as observed in healthy newborns from several European countries, is about 20fold higher than expected on the basis of the observed number of symptomatic homocystinuria patients carrying this mutation, implying clinical underascertainment. The c.833C mutation is also present in combination with a 68-bp insertion, c.[833C, 844_845ins68], in a substantial proportion of chromosomes from nonhomocystinuric individuals worldwide
additional information
structural insights into pathogenic mutations
additional information
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structural insights into pathogenic mutations
additional information
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a 68 bp CBS insertion polymorphism in exon 8 is associated with decreased enzyme activity
additional information
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homocysteine levels in 5,10-methylenetetrahydrofolate reductase 677TT homozygotes who carry the cystathionine beta-synthase 844ins68 allele are significantly lower than in those who do not
additional information
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mutations in the cystathionine beta-synthase gene lead to markedly elevated levels of circulating plasma homocysteine-thiolactone
additional information
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construction of a cobalt CBS, CoCBS, by metalloporphyrin replacement, which results in a high yield of fully active, high purity enzyme, in which heme is substituted by Co-protoporphyrin IX, CoPPIX. The enzyme contains 92% cobalt and 8% iron. CoCBS is indistinguishable from wild-type FeCBS in its activity, tetrameric oligomerization, PLP saturation and responsiveness to the allosteric activator, S-adenosyl-L-methionine
additional information
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effects of delta-aminolevulinic acid, betaine, glycerol and taurine on amounts of tetramers/oligomers of the cystathionine beta-synthase mutants, overview
additional information
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generation of a truncated 45 kDa CBS, 45CBS, enzyme lacking the C-terminal regulatory domain, amino acids 1-413. The wild-type CBS exhibits lower resistance to urea-induced denaturation and lower degree of unfolding cooperativity compared to 45CBS. Proteolytic kinetics by thermolysin under native conditions reveals slower cleavage of wild-type CBS compared to the mutant 45CBS
additional information
removal of the loop of residues 516-525 functionally eliminates the high affinity sites responsible for kinetic stabilization of the full-length enzyme and yields a dimeric AdoMet-inducible enzyme, in which kinetic stabilization is now exerted by AdoMet binding to the remaining low affinity sites
additional information
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removal of the loop of residues 516-525 functionally eliminates the high affinity sites responsible for kinetic stabilization of the full-length enzyme and yields a dimeric AdoMet-inducible enzyme, in which kinetic stabilization is now exerted by AdoMet binding to the remaining low affinity sites
additional information
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CBS activity in liver homogenates is reduced and plasma homocysteine levels are elevated in the CBS heterozygous knockout , CBS-/+ animals compared to wild-type littermate control mice. H2S is also significantly reduced by 30% and 46% compared to wild type in male and female CBS-/+ animals respectively
additional information
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C-terminal regulatory domain deletion leads to formation of highly active dimeric enzyme
additional information
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truncated version residues 1-353 is catalytically active and binds pyridoxal phosphate, removal of residues 354-507 increases the specific activity and alters steady-state kinetic parameters
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