Information on EC 4.2.1.22 - cystathionine beta-synthase

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The expected taxonomic range for this enzyme is: Archaea, Eukaryota, Bacteria

EC NUMBER
COMMENTARY hide
4.2.1.22
-
RECOMMENDED NAME
GeneOntology No.
cystathionine beta-synthase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-serine + L-homocysteine = L-cystathionine + H2O
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C-S bond formation
-
-
-
-
elimination
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
homocysteine and cysteine interconversion
-
-
hydrogen sulfide biosynthesis II (mammalian)
-
-
L-cysteine biosynthesis III (from L-homocysteine)
-
-
L-cysteine biosynthesis VI (from L-methionine)
-
-
cysteine metabolism
-
-
Glycine, serine and threonine metabolism
-
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Cysteine and methionine metabolism
-
-
Metabolic pathways
-
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Biosynthesis of antibiotics
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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.
CAS REGISTRY NUMBER
COMMENTARY hide
9023-99-8
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cystathionine beta-synthase
UniProt
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
vervet monkey
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-
Manually annotated by BRENDA team
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-
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Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
stump-tailed macaque
-
-
Manually annotated by BRENDA team
long-tailed macaque
-
-
Manually annotated by BRENDA team
japanese macaque
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
crested gibbon
-
-
Manually annotated by BRENDA team
Northern white-cheeked gibbon
-
-
Manually annotated by BRENDA team
Bonobo-pygmy chimpanzee
-
-
Manually annotated by BRENDA team
common chimpanzee
-
-
Manually annotated by BRENDA team
Hamadryas baboon
-
-
Manually annotated by BRENDA team
orang utan
-
-
Manually annotated by BRENDA team
Steinernema bibionis
-
-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
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-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
-
cystathionine beta-synthase belongs to the fold II family of pyridoxal 5'-phosphate enzymes
malfunction
metabolism
physiological function
additional information
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
beta-Chloro-DL-alanine + DL-homocysteine
?
show the reaction diagram
-
-
-
-
-
beta-Cyano-DL-alanine + DL-homocysteine
?
show the reaction diagram
-
-
-
-
-
cysteine + ?
H2S + ?
show the reaction diagram
DL-Serine-O-sulfate + DL-homocysteine
?
show the reaction diagram
-
-
-
-
-
L-allothreonine + homocysteine
? + H2O
show the reaction diagram
-
-
-
?
L-Cysteine + 1-butanethiol
?
show the reaction diagram
L-Cysteine + 1-mercapto-2-propanol
HOOC-CH(NH2)-CH2-S-CH2-CH(OH)-CH3 + H2S
show the reaction diagram
L-Cysteine + 1-pentanethiol
?
show the reaction diagram
L-Cysteine + 2-mercaptoethanol
HOOC-CH(NH2)-CH2-S-CH2-CH2OH + H2S
show the reaction diagram
L-cysteine + 2-mercaptoethanol
S-hydroxyethyl-L-cysteine + H2S
show the reaction diagram
-
-
-
?
L-Cysteine + cysteamine
?
show the reaction diagram
L-Cysteine + dithioerythritol
?
show the reaction diagram
L-Cysteine + dithiothreitol
?
show the reaction diagram
L-Cysteine + DL-homocysteine
Cystathionine + H2S
show the reaction diagram
L-cysteine + L-homocysteine
L-cystathionine + H2S
show the reaction diagram
L-Cysteine + monothioglycerol
?
show the reaction diagram
L-serine + cysteamine
L-thialysine
show the reaction diagram
-
-
-
-
?
L-serine + H2O
NH3 + pyruvate
show the reaction diagram
-
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 + homocysteine
?
show the reaction diagram
L-Serine + homocysteine
Cystathionine + H2O
show the reaction diagram
L-Serine + HS-
Cysteine + OH-
show the reaction diagram
L-serine + L-cysteine
?
show the reaction diagram
-
-
-
-
?
L-serine + L-homocysteine
?
show the reaction diagram
-
-
-
-
r
L-serine + L-homocysteine
cystathionine + H2O
show the reaction diagram
L-serine + L-homocysteine
L-cystathionine + H2O
show the reaction diagram
O-acetyl-L-serine + L-homocysteine
?
show the reaction diagram
-
poor substrate for both the wild type and the N- and C-terminally truncated enzyme 71–400 CBS
-
-
?
S-Methyl-L-cysteine + DL-homocysteine
?
show the reaction diagram
-
-
-
-
-
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-Serine + homocysteine
?
show the reaction diagram
L-serine + L-homocysteine
cystathionine + H2O
show the reaction diagram
L-serine + L-homocysteine
L-cystathionine + H2O
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
pyridoxal 5'-phosphate
S-adenosyl-L-methionine
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
contains 0.38 Ca atoms/subunit
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
Fe3+
-
-
Zn2+
-
contains 0.35 Zn atoms/subunit
additional information
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,4-Dichlorophenol
alizarin
Amino-oxyacetate
-
complete inhibition at 0.05 mM
aminooxyacetic acid
beta-chloro-L-alanine
-
-
Bithionol
carbon monoxide
closantel
Co3+
-
Co3+ has 30-60% of the specific activity of Fe3+-CBS
cyanide
-
-
Dichlorophene
Dithionite
-
2fold decrease in enzyme activity due to altered oxidation state of the heme
ellagic acid
Hexachlorophene
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
HgCl2
hydroxylamine
iodoacetate
-
-
L-cystathione
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product inhibition
L-homocysteine
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substrate inhibition
Mn3+
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Mn3+ has 30-60% of the specific activity of Fe3+-CBS
nitric oxide
p-chloromercuribenzoate
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peroxynitrite
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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
Purpurogallin
quercetin
Rafoxanide
regulatory domain
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exerts an inhibitory effect on the enzyme, deletion is correlated with a 1fold increase in catalytic activity
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titanium citrate
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2fold decrease in enzyme activity due to altered oxidation state of the heme
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
AdoMet
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allosteric regulator, 1mol per mole of monomeric subunit activates the enzyme 2fold
betaine
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activates, effects on wild-type and mutant enzymes, overview
delta-aminolevulinic acid
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activates, effects on wild-type and mutant enzymes, overview
Ethionine
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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
glycerol
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activates, effects on wild-type and mutant enzymes, overview
heme
-
regulatory role
pyridoxal 5'-phosphate
S-adenosyl-L-methionine
S-adenosylhomocysteine
-
stimulates activity 1.1fold at 0.48 mM
sinefungin
-
stimulates activity 1.28fold at 1 mM
sodium nitroprusside
-
enhances activity by interacting with cysteine residues, N-ethylmaleimide abolishes this effect
tumor necrosis factor-alpha
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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
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additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.72 - 24
2-mercaptoethanol
5.6 - 6.6
cysteamine
68
DL-homocysteine
-
cosubstrate L-Ser
0.05 - 67
homocysteine
0.13 - 36
L-Cys
0.083 - 0.9
L-cystathionine
2 - 6.11
L-cysteine
0.16 - 5
L-homocysteine
0.91 - 8
L-Ser
0.7 - 27.1
L-serine
additional information
additional information
-
pre-steady-state kinetic analysis of enzyme-monitored turnover during cystathionine beta-synthase-catalyzed H2S generation, overview
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.9 - 34
homocysteine
0.0045 - 6.08
L-cystathionine
0.04 - 4.39
L-cysteine
0.024 - 21.5
L-homocysteine
0.052 - 45
L-serine
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-
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.005 - 7.5
L-cystathionine
6.3 - 80
L-homocysteine
0.031 - 25
L-serine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.6
CO
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37°C under anaerobic conditions
2.3
cyanide
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37°C
2.1
L-homocysteine
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recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
0.32
NO
-
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.15
peroxynitrite
Homo sapiens;
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-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.045
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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
1.3
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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
2.3
-
wild-type enzyme
2.31
-
without pyridoxal 5'-phosphate, without S-adenosyl-L-methionine, mutant H67A
2.6
-
-
2.65
-
wild-type enzyme in the presence of S-adenosyl-L-methionine
2.8
-
full-length ferrous wild type enzyme, at 37°C and pH 8
3.17
-
recombinant 6-His-tagged enzyme after purification, in 50 mM Tris (pH 8.6), at 25°C
3.5
-
-
3.6
-
without pyridoxal 5'-phosphate, without S-adenosyl-L-methionine, wild-type
3.8
-
truncated ferrous mutant enzyme R224A, at 37°C and pH 8
3.9
-
with pyridoxal 5'-phosphate, with S-adenosyl-L-methionine, mutant R266M
3.95
-
D144N mutant in the presence of S-adenosyl-L-methionine
4
-
truncated ferric mutant enzyme R51A, at 37°C and pH 8
4.6
-
recombinant enzyme
5.6
-
-
5.71
-
with pyridoxal 5'-phosphate, with S-adenosyl-L-methionine, mutant R266K
6
-
truncated ferric mutant enzyme R224A, at 37°C and pH 8
8
-
truncated ferrous wild type enzyme, at 37°C and pH 8
10.3
-
full-length ferric wild type enzyme, at 37°C and pH 8
105.2
-
purified recombinant CoCBS, pH 8.6, 37°C
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.4
-
cystathionine beta-synthase assay at
7.9 - 8.3
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enzyme form alpha
8.4 - 9
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 10.5
-
-
6.5 - 10
-
-
6.5 - 9.5
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activity increases with increasing pH, C52S and H65R mutant
6.5 - 10
-
-
7.2 - 9.3
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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
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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)
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
wild-type CBS is therminally activated at 55°C
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
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
Manually annotated by BRENDA team
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cystathionine beta-synthase is associated with the generation and/or differentiation of the radial glia/astrocyte lineage cells in the developing central nervous system
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
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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
Manually annotated by BRENDA team
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-
Manually annotated by BRENDA team
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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
Manually annotated by BRENDA team
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cystathionine beta-synthase activities in wild-type individuals, and in hetero-, and homozygote cystathionine beta-synthase mutants, overview
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
sumoylated CBS is present in the nucleus where it is associated with the nuclear scaffold
Manually annotated by BRENDA team
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);
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
19700
-
2 * 19700, calculated from sequence
20200
-
3 * 20200, calculated from sequence
20300
-
2 * 20300, calculated from sequence
36800
-
gel filtration
38000
-
gel filtration
50000 - 130000
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existence in multiple molecular forms of MW 50000-130000, 235000, 500000, gel filtration
61000
-
4 * 61000
62800
-
gel filtration
65000
-
x * 65000, SDS-PAGE
70000
-
gel filtration, truncated enzyme, dimer
94000
-
gel filtration
100000
-
aged enzyme extract, gel filtration
115000
-
aged enzyme extract, gel filtration
119000
-
fresh enzyme extract, gel filtration
235000
250000
288000
-
fresh and aged enzyme extract, gel filtration
290000
-
fresh enzyme extract, gel filtration
400000
-
gel filtration, truncated enzyme, octamer
486000
-
octamer, gel filtration
500000
-
existence in multiple molecular forms of MW 50000-130000, 235000, 500000, gel filtration
1330000
-
multimer, gel filtration
additional information
-
high tendency for aggregation
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
-
truncated CBS, X-ray crystallography
homotetramer
multimer
octamer
oligomer
-
full length subunits for tetramers and higher oligomers
tetramer
trimer
-
3 * 20200, calculated from sequence
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM