HOME
login
history
all enzymes
BRENDA home
History
Enzyme Nomenclature
Information on EC 4.2.1.22 - cystathionine beta-synthase
for references in articles please use BRENDA:EC4.2.1.22
Word Map on EC 4.2.1.22
- 4.2.1.22
- sulfide
- h2s
- homocystinuria
- hyperhomocysteinemia
- vascular
- mthfr
- candida
- artery
- folate
-
carotid
- cardiovascular
-
transsulfuration
-
corticobasal
-
cajal
- methylenetetrahydrofolate
-
spacers
- nahs
- s-adenosylmethionine
-
subcitrate
-
bismuth
-
colloidal
-
charles
-
gamma-lyase
- hallucinations
-
remethylation
- pyridoxine
-
anamorphic
-
folic
-
supranuclear
-
chemoreceptor
-
thromboembolic
- palsy
-
frontotemporal
-
aminooxyacetic
- apraxia
- stipitis
-
gasotransmitter
-
snrnps
- ascospore
- 3-mercaptopyruvate
- marxianus
-
sulfurtransferase
-
adenosyltransferase
- 5,10-methylenetetrahydrofolate
-
plp-dependent
- o-acetylserine
- malassezia
-
fibrillarin
-
voxel-based
- hydrosulfide
- diagnostics
- analysis
- medicine
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
The expected taxonomic range for this enzyme is: Archaea, Eukaryota, Bacteria
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
EC NUMBER 
COMMENTARY 
4.2.1.22
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
RECOMMENDED NAME
GeneOntology No.
cystathionine beta-synthase
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-serine + L-homocysteine = L-cystathionine + H2O
sequential bisubstrate mechanism in which no product release occurs until both substrates are bound to the enzyme to form a ternary complex
Steinernema bibionis
-
L-serine + L-homocysteine = L-cystathionine + H2O
sequential bisubstrate mechanism in which no product release occurs until both substrates are bound to the enzyme to form a ternary complex
-
L-serine + L-homocysteine = L-cystathionine + H2O
mechanism
-
L-serine + L-homocysteine = L-cystathionine + H2O
ping-pong mechanism
-
L-serine + L-homocysteine = L-cystathionine + H2O
carbanion and aminacrylate intermediates in the CBS-catalyzed reaction, arrangement of the protein residues and pyridoxal 5'-phosphate cofactor in the active site pocket, and reaction mechanism, overview
L-serine + L-homocysteine = L-cystathionine + H2O
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C-S bond formation
-
-
-
-
elimination
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYSTEMATIC NAME
IUBMB Comments
L-serine hydro-lyase (adding homocysteine; L-cystathionine-forming)
A pyridoxal-phosphate protein. A multifunctional enzyme: catalyses beta-replacement reactions between L-serine, L-cysteine, cysteine thioethers, or some other beta-substituted alpha-L-amino acids, and a variety of mercaptans.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
9023-99-8
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
5584, 5586, 5587, 5588, 5591, 5592, 5600, 5601, 5602, 5604, 5605, 649254, 649570, 649869, 649888, 649914, 650017, 650105, 650154, 650408, 652112, 652127, 652339, 652381, 652694, 652695, 663623, 664609, 665132, 677496, 677837, 678140, 678163, 678239, 678269, 680083, 680084, 680085, 681956, 682533, 686517, 687896, 696253, 697295, 697850, 698182, 698850, 701064, 701750, 704177, 704610, 704664, 704793, 704974, 705345, 706024, 706620, 713958, 714179, 714912, 715808, 715809, 728933, 728945, 730143, 730146, 730755
-
-
-
UniProt
a cobalt-substituted variant of hCBS, i.e. Co hCBS, in which CoPPIX replaces FePPIX, i.e. heme
-
-
gene mutations in Venezuelan patients: G85R, T191M, D234N, D444N and Q243X. The mutations present in each country differ from each other depending on the demographic profile
-
-
moderate to intermediate murine model of hyperhomocysteinaemia. Using wild type and heterozygous cystathionine beta-synthase deficient mice fed a methionine enriched diet or a control diet
-
-
mouse model for spontaneous steatohepatitis in which the gene for the MAT1A isoenzyme encoding AdoMet synthetase has been disrupted
-
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
-
cystathionine beta-synthase belongs to the fold II family of pyridoxal 5'-phosphate enzymes
malfunction
metabolism
physiological function
additional information
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
-
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
-
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
-
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
-
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
-
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
-
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 involved in the cysteine pathway of bacteria and plants, overview
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 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 catalyzes the first step in the transsulfuration pathway in mammals, i.e. the condensation of serine and homocysteine to produce cystathionine and water
metabolism
-
CBS is a key enzyme in the trans-sulfuration pathway and catalyzes the condensation of serine with homocysteine to produce cystathionine
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
-
enzyme overexpression extends lifespan of human endothelial cells
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
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
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
-
?
O-acetyl-L-serine + L-homocysteine
?
-
poor substrate for both the wild type and the N- and C-terminally truncated enzyme 71–400 CBS
-
-
?
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 + 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 + DL-homocysteine
Cystathionine + H2S
-
full-length enzyme and truncated enzyme form lacking the C-terminal regulatory domain
-
-
?
L-Serine + homocysteine
?
-
-
-
-
-
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
?
-
initial step in transsulfuration forming cysteine. Homocysteine is a relatively toxic amino acid, which levels have to be kept low
-
-
-
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
-
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 + 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
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
-
-
696253, 696822, 697295, 698182, 698850, 701064, 704664, 714179, 714912, 715808, 715809, 728933, 728945, 730143, 730146, 730755
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
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
?
-
-
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
?
-
-
the enzyme performs L-cysteine sythesis from L-serine
-
-
-
additional information
?
-
-
the enzyme performs L-cysteine sythesis from L-serine
-
-
-
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
?
-
-
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 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
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-Serine + homocysteine
?
-
-
-
-
-
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
?
-
initial step in transsulfuration forming cysteine. Homocysteine is a relatively toxic amino acid, which levels have to be kept low
-
-
-
L-serine + L-homocysteine
cystathionine + H2O
Q91WT9
the enzyme participates in the process of oocyte maturation
-
-
?
L-serine + L-homocysteine
L-cystathionine + H2O
-
-
-
-
?
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
?
-
-
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
?
-
-
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
?
-
-
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
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
heme
-
the heme favors the ferric state at lower pH and, in the presence of reductants, attains the ferric state via transient formation of the ferrous state. Fe(II)-enzyme and Fe(III)-enzyme are apparently interconverted by a proton-controlled internal electron transfer process
heme
-
carbon monoxide or nitric oxide can bind to the cofactor, resulting in enzyme inhibition
heme
-
the in vitro activity of cystathionine beta-synthase is sensitive to the redox state of the heme and is higher in the ferric form. Both carbon monoxide and nitric oxide bind to ferrous heme and inhibit the enzyme. The crystal structure of the protein reveals that the heme is about 20 A away from the active site
heme
-
heme in CBS is six-coordinate, low spin, and contains cysteine and histidine as axial ligands, the unusual heme in CBS represents a potential source of cytosolic superoxide radical
heme
-
the specific activity of CBS improves 1.8-2.8fold under truncation of R51A and R224A when the heme iron is in the ferric state
heme
-
the specific activity of the alkaline form is approximately 25% of that for the intact CBS enzyme when the heme iron is in the ferric state
heme
-
requires a heme cofactor for maximal activity, heme plays a key role in proper CBS folding and assembly
heme
-
vibrational coherence spectroscopy is used to probe the low-frequency vibrational motions of the heme and how they depend on structural distortions that are induced by the CBS protein environment
heme
-
-
649869, 649888, 649914, 650105, 650154, 652551, 652695, 681230, 697850, 701064, 701929, 704974, 713958, 714071, 715172, 729799
pyridoxal 5'-phosphate
-
Lys119 is eesential for the formation of the internal aldimine with pyridoxal 5'-phosphate
pyridoxal 5'-phosphate
-
forms a series of intermediates during the reaction, gem-diamine and external aldimine of aminoacrylate are the primary intermediates in the forward half-reaction with L-serine and the external aldimine of aminoacrylate or its complex with L-homocysteine is the primary intermediate in the reverse half-reaction with L-cystathionine
pyridoxal 5'-phosphate
-
reacts with L-allothreonine to form a stable 3-methyl aminoacrylate intermediate
pyridoxal 5'-phosphate
-
Km-value for wild-type enzyme: 0.00118 mM, KM-value for mutant enzyme I278T: 0.00084 mM, KM-value for mutant enzyme R266K: 0.00339 mM
pyridoxal 5'-phosphate
-
i.e. PLP, serves in the catalytic chemistry of CBS via a well-established mechanism
pyridoxal 5'-phosphate
-
-
649869, 649914, 650096, 650105, 650154, 652695, 664020, 682076, 686517, 687896, 696253, 696822, 697295, 697850, 698182, 701064, 701750, 701929, 704177, 704974, 705345, 706024, 706620, 714071, 714179, 714912, 715150, 715172, 715808, 715809
S-adenosyl-L-methionine
-
allosterical regulation, increase of the enzyme's affinity for homocysteine
additional information
-
yeast cystathionine beta-synthase does not have a heme cofactor
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
-
97.1% Fe2+ and 2.9% Co2+ in wild-type FeCBS enzyme, 8% Fe2+ and 92% Co2+ in the CoCBS enzyme variant
Co3+
-
cobalt-substituted variant of hCBS, i.e. Co hCBS, in which CoPPIX replaces FePPIX, i.e. heme. Co(III) hCBS is a unique Co-substituted heme protein: the Co(III) ion is 6-coordinate, low-spin, diamagnetic, and bears a cysteine(thiolate) as one of its axial ligands. Electronic absorption and MCD spectra of the Co-substituted heme protein, overview. Co(III) hCBS is slowly reduced to Co(II) hCBS, which contains a 5-coordinate, low-spin, S = 1/2 Co-porphyrin that does not retain the cysteine(thiolate) ligand. This form of Co(II)hCBS binds NO but not CO. Co(II) hCBS is reoxidized in the air to form a new Co(III) form, which does not contain a cysteine(thiolate) ligand. Maintaining the native heme ligation motif of wild-type Fe hCBS (Cys/His) is essential in maintaining maximal activity in Co hCBS
Fe
Fe2+
Zn
additional information
Fe2+
-
ferrous human cystathionine beta-synthase loses activity during enzyme assay due to a ligand switch process
Fe2+
-
heme enzyme, 97.1% Fe2+ and 2.9% Co2+ in wild-type FeCBS enzyme, 8% Fe2+ and 92% Co2+ in the CoCBS enzyme variant
additional information
-
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
-
maintaining the native heme ligation motif of wild-type Fe hCBS (Cys/His) is essential in maintaining maximal activity in Co hCBS
additional information
-
Na+, K+, Li+, Ca2+, Mg2+, Zn2+, Co2+, no effect on activity
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Dithionite
-
2fold decrease in enzyme activity due to altered oxidation state of the heme
Hg2+
-
reactivity of Co(III) hCBS with HgCl2 is consistent with a loss of the cysteine(thiolate) ligand. 2-Mercaptoethanol is unable to reverse the Hg-induced ligand switch, in contrast to some other heme-thiolate proteins
peroxynitrite
-
exposure to peroxynitrite does not modify bound pyridoxal 5'-phosphate but leads to nitration of Trp208, Trp43 and Tyr223 and alterations in the heme environment including loss of thiolate coordination, conversion to high-spin and bleaching, with no detectable formation of oxoferryl compounds nor promotion of one-electron processes
regulatory domain
-
exerts an inhibitory effect on the enzyme, deletion is correlated with a 1fold increase in catalytic activity
-
titanium citrate
-
2fold decrease in enzyme activity due to altered oxidation state of the heme
-
carbon monoxide
-
binds to the prosthetic heme, stabilizing 6-coordinated CO-Fe(II)-histidine complex to block the activity
carbon monoxide
-
binds to the prosthetic heme, stabilizing 6-coordinated CO-Fe(II)-histidine complex to block the activity
CO
-
reversible competitive with respect to homocysteine, complete loss of activity at 0.06 mM
CO
-
can bind to the cofactor heme, resulting in enzyme inhibition. CBS exhibits strong anticooperativity in CO binding
CO
-
CO binding is found to induce a tautomeric shift of the pyridoxal 5'-phosphate from the ketoenamine to the enolimine form. The ketoenamine is key to pyridoxal 5'-phosphate reactivity because its imine C-N bond is protonated, facilitating attack by the nucleophilic substrate, serine
additional information
-
the alternation of heme environment inactivates the enzyme
-
additional information
-
taurine activates some cystathionine beta-synthase mutants slightly, while it slightly inhibits the wild-type enzyme and other cystathionine beta-synthase mutants
-
additional information
-
the CBS activity is significantly reduced in kidneys subjected to ischemia alone (15-60 min) or subjected to ischemia followed by reperfusion for 1-24 h, injection of alkaline solution into the kidney partially restores the CBS activity during ischemia, reduction of CBS activity during reperfusion is accompanied by an elevation of nitrate and nitrite in the kidney tissue, injection of 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide restores the CBS activity in the kidneys subjected to ischemia-reperfusion
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
AdoMet
-
allosteric regulator, 1mol per mole of monomeric subunit activates the enzyme 2fold
delta-aminolevulinic acid
-
activates, effects on wild-type and mutant enzymes, overview
Ethionine
-
i.e. 2-amino-4-(ethylthio)butyric acid, an methionine analogue, which is converted to S-adenosyl-ethionine in vivo and activates CBS, treatment increased liver CBS activity 4.0fold in wild-type mice
sodium nitroprusside
-
enhances activity by interacting with cysteine residues, N-ethylmaleimide abolishes this effect
tumor necrosis factor-alpha
-
leads to cleavage of the enzyme to a truncated form and therefore increases the activity, 50% increase of activity after treatment of HepG2 cells for 16 h
-
S-adenosyl-L-methionine
structure of the regulatory, energy-sensing CBS domains and mechanism for allosteric activation by S-adenoyl-L-methionine, overview
S-adenosyl-L-methionine
-
activates full length enzyme, but not the truncated core, 4 S-adenosyl-L-methionine molecules per tetramer
S-adenosyl-L-methionine
-
3fold activation, allosteric regulator of the full length enzyme, does not activate the truncated enzyme
S-adenosyl-L-methionine
-
the enzyme is allosterically activated by S-adenosyl-L-methionine under normal conditions but is destabilized under pathological conditions
S-adenosyl-L-methionine
-
about 4fold increase of specific activity in the presence of 0.25 mM S-adenosyl-L-methionine
S-adenosyl-L-methionine
-
allosteric activator. Binding of AdoMet to wild-type CBS moderately increases the protein stability toward urea, while it does not influence the unfolding cooperativity
S-adenosyl-L-methionine
-
the addition of S-adenosyl-L-methionine nearly doubles enzyme activity
S-adenosyl-L-methionine
-
the enzyme is allosterically activated (2-3fold) by S-adenosyl-L-methionine
S-adenosyl-L-methionine
-
the enzyme is allosterically activated by S-adenosyl-L-methionine under normal conditions but is destabilized under pathological conditions
additional information
-
treatment with 0.2 M trimethylamine-N-oxide results in rescuing expression as well as activity of CBS to 82% of human wild type CBS produced in a yeast heme-deficient strain
-
additional information
-
taurine activates some cystathionine beta-synthase mutants slightly, while it slightly inhibits the wild-type enzyme and other cystathionine beta-synthase mutants
-
additional information
-
oxidizing conditions increase the enzyme activity by 2fold
-
additional information
-
S-adenosyl-L-methionine does not activate
-
additional information
-
enzyme can not be activated by S-adenosyl-L-methionine
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
pre-steady-state kinetic analysis of enzyme-monitored turnover during cystathionine beta-synthase-catalyzed H2S generation, overview
-
7.17
homocysteine
-
37°C, pH 8.6, mutant enzyme R266K; 37°C, pH 8.6, wild-type enzyme
15
homocysteine
-
pH 6.8, 37°C, full length enzyme after homocysteine pre-treatment
67
homocysteine
-
pH 6.8, 37°C, deltaC143 mutant after homocysteine pre-treatment
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
0.43
L-homocysteine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
1.04
L-homocysteine
-
37°C, pH 8.0, wild-type enzyme, without S-adenosyl-L-methionine
1.1
L-homocysteine
-
mutant enzyme S466L, in the presence of 0.25 mM S-adenosyl-L-methionine
2.5
L-homocysteine
-
wild type enzyme, in the presence of 0.25 mM S-adenosyl-L-methionine
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
5.5
L-serine
-
pH 6.8, 37°C, full length enzyme after homocysteine pre-treatment
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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-
-
0.0045
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), mutant S289A
1.03
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), wild-type
0.024
L-homocysteine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
3.3
L-homocysteine
-
37°C, pH 8.0, wild-type enzyme, without S-adenosyl-L-methionine
4.66
L-homocysteine
-
37°C, pH 8.0, wild-type enzyme, without S-adenosyl-L-methionine
12.7
L-homocysteine
-
37°C, pH 8.0, wild-type enzyme, with S-adenosyl-L-methionine
1.67
L-serine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.005
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), mutant S289A
7.5
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), wild-type
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.1
L-homocysteine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.045
-
recombinant 6-His-tagged enzyme from crude extract, in 50 mM Tris (pH 8.6), at 25°C
0.68
-
without pyridoxal 5'-phosphate, without S-adenosyl-L-methionine, mutant R266M
1.2
1.3
-
full-length ferrous mutant enzyme R224A, at 37°C and pH 8; full-length ferrous mutant enzyme R51A, at 37°C and pH 8
1.91
-
without pyridoxal 5'-phosphate, without S-adenosyl-L-methionine, mutant R266K
2.2
-
full-length ferric mutant enzyme R224A, at 37°C and pH 8; full-length ferric mutant enzyme R51A, at 37°C and pH 8
2.31
-
without pyridoxal 5'-phosphate, without S-adenosyl-L-methionine, mutant H67A
3.17
-
recombinant 6-His-tagged enzyme after purification, in 50 mM Tris (pH 8.6), at 25°C
3.6
-
without pyridoxal 5'-phosphate, without S-adenosyl-L-methionine, wild-type
5.2
additional information
5.2
-
with pyridoxal 5'-phosphate, with S-adenosyl-L-methionine, mutant H67A; with pyridoxal 5'-phosphate, with S-adenosyl-L-methionine, wild-type
additional information
-
continous spectrometric assay for cystathionine beta-synthase
additional information
-
specific activities of wild-type and mutants in presence of activators, overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
8.3
8.5
8.6
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.2 - 9.3
-
pH 7.2: about 45% of maximal activity, pH 9.3: about 75% of maximal activity, full-length Fe(III)-enzyme and truncated Fe(III) CBS-45
7.3 - 9.5
-
pH 7.3: about 45% of maximal activity, pH 9.5: about 80% of maximal activity, full-length and the C-terminally truncated enzyme (CBS 1-413)
8.3 - 9.5
-
pH 8.3: about 45% of maximal activity, pH 9.5: about 85% of maximal activity N- and C-terminally truncated enzyme (BS 71-400)
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
cystathionine beta-synthase is associated with the generation and/or differentiation of the radial glia/astrocyte lineage cells in the developing central nervous system
-
cystathionine beta-synthase is associated with the generation and/or differentiation of the radial glia/astrocyte lineage cells in the developing central nervous system
-
highest cystathionine beta-synthase protein presence in cornea, conjunctiva and iris, followed by retina and optic nerve. Cystathionine beta-synthase may be a oxidative defense enzyme in the eye tissue, in particular in the segments of the eye where constant environmental oxidative stress is imposed
-
ubiquitously expressed in the ovary with the strongest expression in follicular cells at all stages. In late antral follicles, cystathionine beta-synthase expression is markedly higher in granulosa cells located close to the antrum and in cumulus cells around the oocyte
-
cystathionine beta-synthase activities in wild-type individuals, and in hetero-, and homozygote cystathionine beta-synthase mutants, overview
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
-
cystathionine beta-synthase is enriched in the brains of Down's syndrome patients
-
cystathionine beta-synthase activity is indistinguishable in females and males
-
cystathionine beta-synthase activity is indistinguishable in females and males
-
cystathionine beta-synthase activity is indistinguishable in females and males
-
higher cystathionine beta-synthase activity in females versus males
-
found in somas in the inner nuclear layer and as punctate staining in the inner and outer plexiform layers in the salamander retina
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
sumoylated CBS is present in the nucleus where it is associated with the nuclear scaffold
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PDB
SCOP
CATH
UNIPROT
ORGANISM
Q83A84
Coxiella burnetii (strain RSA 493 / Nine Mile phase I);
Drosophila melanogaster;
Homo sapiens;
Lactobacillus plantarum (strain ATCC BAA-793 / NCIMB 8826 / WCFS1);
Saccharomyces cerevisiae (strain ATCC 204508 / S288c);
F9UT54
Lactobacillus plantarum (strain ATCC BAA-793 / NCIMB 8826 / WCFS1);
F9UT54
Lactobacillus plantarum (strain ATCC BAA-793 / NCIMB 8826 / WCFS1);
P32582
Saccharomyces cerevisiae (strain ATCC 204508 / S288c);
P32582
Saccharomyces cerevisiae (strain ATCC 204508 / S288c);
P32582
Saccharomyces cerevisiae (strain ATCC 204508 / S288c);
P32582
Saccharomyces cerevisiae (strain ATCC 204508 / S288c);
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
45000
48000
50000 - 130000
-
existence in multiple molecular forms of MW 50000-130000, 235000, 500000, gel filtration
55000
63000
68000
235000
250000
500000
-
existence in multiple molecular forms of MW 50000-130000, 235000, 500000, gel filtration
48000
-
2 * 48000, proteolytically activated enzyme, derived from 4 * 68000 enzyme, SDS-PAGE
48000
-
2 * 48000, proteolytically activated enzyme, derived from 4 * 68000 enzyme, SDS-PAGE
68000
-
2 * 48000, proteolytically activated enzyme, derived from 4 * 68000 enzyme, SDS-PAGE; 4 * 68000, enzyme from fresh liver extract, SDS-PAGE
68000
-
2 * 48000, proteolytically activated enzyme, derived from 4 * 68000 enzyme, SDS-PAGE; 4 * 68000, enzyme from fresh liver extract, SDS-PAGE
235000
-
existence in multiple molecular forms of MW 50000-130000, 235000, 500000, gel filtration
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homotetramer
multimer
octamer
tetramer
additional information
dimer
-
2 * 48000, proteolytically activated enzyme, derived from 4 * 68000 enzyme, SDS-PAGE
dimer
-
2 * 45000 Da, truncated human CBS lacking 143 amino acids at the C-terminus
dimer
-
2 * 48000, proteolytically activated enzyme, derived from 4 * 68000 enzyme, SDS-PAGE
additional information
-
mutant enzymes K102N and P78R/K102N behaves like wild-type enzyme by native gel chromatography and exist as a mixture of higher-order quaternary states
additional information
-
each subunit has a modular structure consisting of three domains: an N-terminal heme binding domain, a highly conserved pyridoxal 5'-phosphate-binding catalytic core, and a S-adenosyl-L-methionine-binding C-terminal regulatory domain
additional information
-
CBS protein comprises three regions: the N-terminal heme-binding domain, residues 1-69, a highly conserved catalytic core, residues 70-413, and the C-terminal regulatory domain, resdiues 414-551, and an autoinhibitory module with binding site for the allosteric activator, S-adenosyl-L-methionine. Computational modeling of CBS structure, the enzyme has a regulatory dimer-dimer interface, homology modeling and protein-protein docking, overview. Model of wild-type CBS dimer by docking of a single C-terminal regulatory domain to mutant 45CBS dimer, PDB ID 1JBQ, and surface mapping of wild-type CBS and mutant 45CBS with diverse differentially reactive amino acid residues involved in conformational changes and thermal activation, overview
additional information
-
three-dimensional CBS structure and molecular dynamics simulation of folding process in CBS wild-type and mutants, overview
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
POSTTRANSLATIONAL MODIFICATION
ORGANISM