BRENDA home
History
Information on EC 4.2.1.22 - cystathionine beta-synthase
for references in articles please use BRENDA:EC4.2.1.22Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
4.2.1.22 cystathionine beta-synthaseIUBMB Comments
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.
Specify your search results
Word Map
- 4.2.1.22
- h2s
- sulfide
- homocystinuria
- hyperhomocysteinemia
-
spacer
- artery
-
corticobasal
- mthfr
-
carotid
- candida
- folate
-
transsulfuration
- conidia
-
cajal
- dextrose
- nahs
- methylenetetrahydrofolate
-
charles
-
anamorphic
-
supranuclear
-
bismuth
- palsy
- hallucinations
-
biodiversity
-
reisolated
-
conidiophore
-
gamma-lyase
-
hyaline
-
remethylation
-
gasotransmitter
- 3-mercaptopyruvate
- ascospore
-
chemoreceptor
-
thromboembolic
- sulfurtransferase
-
frontotemporal
-
snrnps
-
aminooxyacetic
-
rinsed
- apraxia
-
visuospatial
- 5,10-methylenetetrahydrofolate
-
voxel-based
- marxianus
- naocl
-
appressoria
- hydrosulfide
-
symptomless
- medicine
- ascus
-
phytopathological
- diagnostics
- analysis
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
Beta-thionase, CBS, CBS424, CDCP2, CNNM2, Cys4, CysB, cystathionine beta synthase, cystathionine beta-synthase, cystathionine beta-synthase domain-containing protein, 
more
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Beta-thionase
-
-
-
-
CBS
Cys4
cystathionine beta-synthase
cystathionine-beta-synthase
Cysteine synthase
-
-
-
-
Hemoprotein H-450
-
-
-
-
Methylcysteine synthase
-
-
-
-
Serine sulfhydrase
-
-
-
-
Serine sulfhydrylase
-
-
-
-
Serine sulphhydrase
-
-
-
-
ytCBS
-
a truncated form of CBS comprising the catalytic core is used for mutational analysis
CBS
-
-
-
-
CBS
-
-
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
mechanism
-
L-serine + L-homocysteine = L-cystathionine + H2O
ping-pong mechanism
-
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
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
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 SOURCE
PATHWAYS
BRENDA
KEGG
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.
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.
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 71â400 CBS
-
-
?
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
Lactiplantibacillus plantarum ATCC BAA-793
-
-
-
?
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 + 2-mercaptoethanol
S-hydroxyethyl-L-cysteine + H2S
-
-
?
L-Cysteine + DL-homocysteine
Cystathionine + H2S
-
full-length enzyme and truncated enzyme form lacking the C-terminal regulatory domain
-
-
?
L-cysteine + L-homocysteine
L-cystathionine + H2S
-
-
-
?
L-cysteine + L-homocysteine
L-cystathionine + H2S
Lactiplantibacillus plantarum ATCC BAA-793
-
-
-
?
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, 697295, 698182, 698850, 701064, 704664, 714179, 714912, 715808, 715809, 728933, 728945, 730143, 730146, 730755
-
-
?
O-acetyl-L-serine + H2S
pyruvate + acetate + NH3
-
-
-
?
O-acetyl-L-serine + L-homocysteine
cystathionine + acetate
-
-
-
?
O-acetyl-L-serine + L-homocysteine
cystathionine + acetate
Lactiplantibacillus plantarum ATCC BAA-793
-
-
-
?
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
?
-
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
?
-
-
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 SUBSTRATE
NATURAL 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 + 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
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
-
-
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
-
requires a heme cofactor for maximal activity, heme plays a key role in proper CBS folding and assembly
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
-
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
enzyme possesses a noncatalytic heme cofactor with cysteine and histidine as ligands. Nitrite is reduced by Fe(II)-CBS to form Fe(II)NO radical-CBS. Reoxidation of Fe(II)NO radical-CBS by O2 shows complex kinetic behavior and leads to peroxynitrite (ONOO-) formation
pyridoxal 5'-phosphate
-
-
649869, 649914, 650105, 650154, 652695, 664020, 686517, 687896, 696253, 697295, 697850, 698182, 701064, 701750, 704177, 704974, 705345, 706024, 706620, 714179, 714912, 715172, 715808, 715809
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
A0A1J9VES8
cofactor is highly flexible due to the active site being wide open
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.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(5Z)-5-[(4-hydroxy-3-methoxyphenyl)methylidene]-3-methyl-2-(methylsulfanyl)-3,5-dihydro-4H-imidazol-4-one
-
compound derived from polyandrocarpamines A and B, i.e. 2-aminoimidazolone compounds isolated from the ascidian Polyandrocarpa sp.
2-methoxy-4-[(Z)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]phenyl acetate
-
compound derived from polyandrocarpamines A and B, i.e. 2-aminoimidazolone compounds isolated from the ascidian Polyandrocarpa sp.
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
3fold activation, allosteric regulator of the full length enzyme, does not activate the truncated enzyme
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
-
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
AdoMet binding significantly enhances CBS inhibition by CO. NO radical binding to reduced CBS i also enhanced by AdoMet, although to a lesser as compared with CO. CO and NOradical binding is unchanged by AdoMet in a truncated form of CBS lacking the C-terminal regulatory domain
S-adenosyl-L-methionine
allosteric activator, in the presence of AdoMet, the autoinhibition exerted by the regulatory region is eliminated
S-adenosyl-L-methionine
half-activation of wild-type at 0.0258 mM, mutant D444N 1.234 mM, mutant S500L 0.063 mM, respectively
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
enzyme is not allosterically regulated by AdoMet
-
additional information
enzyme is more active under oxidizing 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
-
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
-
4.7
H2S
cosubstrate L-serine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
0.08
homocysteine
-
wild-type enzyme, 37°C, presence of S-adenosyl-L-methionine
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
3
L-cysteine
formation of L-cystathionine, mutant A70S, pH 7.5, 37°C
5.9
L-cysteine
formation of L-cystathionine, wild-type, pH 7.5, 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
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
0.29
L-homocysteine
wild-type, 37°C, pH not specified in the publication
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
1.1
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
4.48
L-homocysteine
cosubstrate L-cysteine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
20
L-homocysteine
formation of L-cystathionine, mutant A70S, pH 7.5, 37°C
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
1.32
L-serine
cosubstrate H2S, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
2.13
L-serine
synthesis of L-cystathionine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
3.7
L-serine
mutant K523Sfs?18, 37°C, pH not specified in the publication
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-
-
0.78
H2S
cosubstrate L-serine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
0.0045
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), mutant S289A
1.03
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), wild-type
0.022
L-cysteine
formation of (2R,2'R)-3,3'-sulfanediylbis(2-aminopropanoic acid), mutant E223G, pH 7.5, 37°C
0.6
L-cysteine
formation of L-cystathionine, mutant E223G, pH 7.5, 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
2
L-cysteine
formation of L-cystathionine, mutant A70S, pH 7.5, 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
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
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
26.78
L-homocysteine
cosubstrate L-cysteine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
0.62
L-serine
cosubstrate H2S, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
1.67
L-serine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
3.67
L-serine
-
37°C, pH 8.0, wild-type enzyme, without S-adenosyl-L-methionine
14.01
L-serine
cosubstrate L-homocysteine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
39
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.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.17
H2S
cosubstrate L-serine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
0.005
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), mutant S289A
7.5
L-cystathionine
-
reverse reaction (L-cystathionine hydrolysis), wild-type
0.0006
L-cysteine
formation of (2R,2'R)-3,3'-sulfanediylbis(2-aminopropanoic acid), mutant E223G, pH 7.5, 37°C
0.12
L-cysteine
formation of (2R,2'R)-3,3'-sulfanediylbis(2-aminopropanoic acid), wild-type, pH 7.5, 37°C
0.18
L-cysteine
cosubstrate H2O, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
1.3
L-cysteine
formation of L-cystathionine, wild-type, pH 7.5, 37°C
1.5
L-cysteine
formation of L-cystathionine, mutant A70S, pH 7.5, 37°C
1.98
L-cysteine
cosubstrate L-homocysteine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
8.9
L-cysteine
formation of L-cystathionine, mutant E223G, pH 7.5, 37°C
0.15
L-homocysteine
formation of L-cystathionine, mutant A70S, pH 7.5, 37°C
0.83
L-homocysteine
formation of L-cystathionine, mutant E223G, pH 7.5, 37°C
2.8
L-homocysteine
mutant D444N, 37°C, pH not specified in the publication
4.71
L-homocysteine
mutant V449G, 37°C, pH not specified in the publication
4.82
L-homocysteine
mutant S500L, 37°C, pH not specified in the publication
5.22
L-homocysteine
mutant K523Sfs?18, 37°C, pH not specified in the publication
5.23
L-homocysteine
mutant P427L, 37°C, pH not specified in the publication
6.02
L-homocysteine
cosubstrate L-cysteine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
10.56
L-homocysteine
A0A1J9VES8
wild-type, production of H2S, pH 8.2, 37°C
11
L-homocysteine
mutant L540Q, 37°C, pH not specified in the publication
12.74
L-homocysteine
synthesis of L-cystathionine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
14
L-homocysteine
formation of L-cystathionine, wild-type, pH 7.5, 37°C
0.47
L-serine
cosubstrate H2S, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
0.71
L-serine
mutant K523Sfs?18, 37°C, pH not specified in the publication
7.61
L-serine
synthesis of L-cystathionine, presence of S-adenosyl-L-methionine, pH 7.4, 37°C
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
3.9
L-homocysteine
mutant K523Sfs?18, 37°C, pH not specified in the publication
7.7
L-homocysteine
mutant P427L, 37°C, pH not specified in the publication
12
L-homocysteine
mutant V449G, 37°C, pH not specified in the publication
12.8
L-homocysteine
mutant L540Q, 37°C, pH not specified in the publication
12.8
L-homocysteine
wild-type, 37°C, pH not specified in the publication
13.4
L-homocysteine
mutant D444N, 37°C, pH not specified in the publication
27.8
L-homocysteine
mutant S500L, 37°C, pH not specified in the publication
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
0.087
(5Z)-5-[(4-hydroxy-3-methoxyphenyl)methylidene]-3-methyl-2-(methylsulfanyl)-3,5-dihydro-4H-imidazol-4-one
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
0.083
2-methoxy-4-[(Z)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]phenyl acetate
Homo sapiens
-
pH not specified in the publication, temperature not specified in the publication
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
1.91
-
without pyridoxal 5'-phosphate, without S-adenosyl-L-methionine, mutant R266K
2.2
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
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
6.5 - 10
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.
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
enzyme shows activities of both EC 4.2.1.22 and 2.5.1.47
A0A1J9VES8
UniProt
brenda
bifunctional cystathionine beta-synthase EC 4.2.1.22 and O-acetyl-L-serine sulfhydrylase, EC 2.5.1.47
UniProt
brenda
Lactiplantibacillus plantarum ATCC BAA-793
bifunctional cystathionine beta-synthase EC 4.2.1.22 and O-acetyl-L-serine sulfhydrylase, EC 2.5.1.47
UniProt
brenda
protein is composed of cystathionine beta-synthase (CBS) and aspartate kinase chorismate mutase tyrA (ACT) domains
UniProt
brenda
-
5584, 5586, 5587, 5588, 5591, 5592, 5600, 5601, 5602, 5604, 5605, 649254, 649570, 649869, 649888, 649914, 650017
-
-
brenda
-
652694, 652695, 663623, 664609, 665132, 677496, 677837, 678140, 678163, 678239, 678269, 680083, 680084, 680085
-
-
brenda
a cobalt-substituted variant of hCBS, i.e. Co hCBS, in which CoPPIX replaces FePPIX, i.e. heme
-
-
brenda
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
-
-
brenda
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
-
-
brenda
mouse model for spontaneous steatohepatitis in which the gene for the MAT1A isoenzyme encoding AdoMet synthetase has been disrupted
-
-
brenda
-
-
-
brenda
-
-
-
brenda
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
brenda
-
cystathionine beta-synthase is associated with the generation and/or differentiation of the radial glia/astrocyte lineage cells in the developing central nervous system
brenda