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Information on EC 4.2.1.22 - cystathionine beta-synthase and Organism(s) Homo sapiens and UniProt Accession P35520

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     4 Lyases
         4.2 Carbon-oxygen lyases
             4.2.1 Hydro-lyases
                4.2.1.22 cystathionine beta-synthase
IUBMB 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.
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Homo sapiens
UNIPROT: P35520
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
cbs, cystathionine beta-synthase, cystathionine-beta-synthase, cnnm2, cystathionine beta synthase, serine sulfhydrylase, ytcbs, serine sulfhydrase, cdcp2, cbs424, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cystathionine beta-synthase
-
Beta-thionase
-
-
-
-
CBS424
-
inactive form of CBS
cystathionine beta-synthase
-
-
cystathionine-beta-synthase
-
-
Cysteine synthase
-
-
-
-
hCBS
-
-
Hemoprotein H-450
-
-
-
-
Methylcysteine synthase
-
-
-
-
Serine sulfhydrase
-
-
-
-
Serine sulfhydrylase
-
-
-
-
Serine sulphhydrase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-serine + L-homocysteine = L-cystathionine + H2O
show the reaction diagram
ping-pong mechanism
L-serine + L-homocysteine = L-cystathionine + H2O
show the reaction diagram
mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
elimination
-
-
-
-
C-S bond formation
-
-
-
-
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
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
L-cysteine
H2S + L-serine
show the reaction diagram
-
-
-
?
L-cysteine + 2-mercaptoethanol
S-hydroxyethyl-L-cysteine + H2S
show the reaction diagram
-
-
?
L-cysteine + L-homocysteine
L-cystathionine + H2S
show the reaction diagram
-
-
-
?
L-cysteine + L-serine
lanthionine + H2O
show the reaction diagram
-
-
-
?
L-serine + H2S
L-cysteine
show the reaction diagram
-
-
-
?
L-Serine + homocysteine
Cystathionine + H2O
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
L-Cysteine + DL-homocysteine
Cystathionine + H2S
show the reaction diagram
-
full-length enzyme and truncated enzyme form lacking the C-terminal regulatory domain
-
-
?
L-cysteine + L-homocysteine
L-cystathionine + H2S
show the reaction diagram
-
-
-
-
r
L-serine + cysteamine
L-thialysine
show the reaction diagram
-
-
-
-
?
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
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
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-serine + L-homocysteine
L-cystathionine + H2O
show the reaction diagram
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
pyridoxal 5'-phosphate
S-adenosyl-L-methionine
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
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
additional information
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
carbon monoxide
-
CO
can bind to the cofactor heme, resulting in enzyme inhibition. CBS exhibits strong anticooperativity in CO binding
L-homocysteine
-
nitric oxide
-
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
(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.
Amino-oxyacetate
-
complete inhibition at 0.05 mM
aminooxyacetic acid
-
-
Co3+
-
Co3+ has 30-60% of the specific activity of Fe3+-CBS
cyanide
-
-
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
L-homocysteine
-
substrate inhibition
Mn3+
-
Mn3+ has 30-60% of the specific activity of Fe3+-CBS
regulatory domain
-
exerts an inhibitory effect on the enzyme, deletion is correlated with a 1fold increase in catalytic activity
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
S-adenosyl-L-methionine
AdoMet
-
allosteric regulator, 1mol per mole of monomeric subunit activates the enzyme 2fold
betaine
-
activates, effects on wild-type and mutant enzymes, overview
delta-aminolevulinic acid
-
activates, effects on wild-type and mutant enzymes, overview
glycerol
-
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
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
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4.7 - 5.02
H2S
8.11 - 15.92
L-cysteine
0.29 - 4.48
L-homocysteine
1.27 - 3.7
L-serine
5.6 - 6.6
cysteamine
0.05 - 67
homocysteine
0.13
L-cystathionine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
2 - 6.11
L-cysteine
0.43 - 5
L-homocysteine
0.91 - 3.1
L-Ser
0.77 - 18
L-serine
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.35 - 0.78
H2S
1.06 - 31.34
L-cysteine
4.66 - 26.78
L-homocysteine
0.39 - 14.01
L-serine
5.9 - 34
homocysteine
0.04 - 4.39
L-cysteine
0.024 - 12.7
L-homocysteine
0.052 - 45
L-serine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.07 - 0.17
H2S
0.13 - 1.98
L-cysteine
1.93 - 12.74
L-homocysteine
0.28 - 7.61
L-serine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.9 - 27.8
L-homocysteine
5.6
CO
-
37°C under anaerobic conditions
2.3
cyanide
-
37°C
2.1
L-homocysteine
-
recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25°C
0.32
NO
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.15
peroxynitrite
Homo sapiens
-
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
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
1.2
truncated ferrous mutant enzyme R51A, at 37°C and pH 8
10.3
full-length ferric wild type enzyme, at 37°C and pH 8
2.8
full-length ferrous wild type enzyme, at 37°C and pH 8
3.8
truncated ferrous mutant enzyme R224A, at 37°C and pH 8
4
truncated ferric mutant enzyme R51A, at 37°C and pH 8
5.2
truncated ferric wild type enzyme, at 37°C and pH 8
6
truncated ferric mutant enzyme R224A, at 37°C and pH 8
8
truncated ferrous wild type enzyme, at 37°C and pH 8
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
1.91
-
without pyridoxal 5'-phosphate, without S-adenosyl-L-methionine, mutant R266K
105.2
-
purified recombinant CoCBS, pH 8.6, 37°C
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
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
3.9
-
with pyridoxal 5'-phosphate, with S-adenosyl-L-methionine, mutant R266M
3.95
-
D144N mutant in the presence of S-adenosyl-L-methionine
4.6
-
recombinant enzyme
5.6
-
-
5.71
-
with pyridoxal 5'-phosphate, with S-adenosyl-L-methionine, mutant R266K
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.3
assay at
8.6
assay at
7.9 - 8.3
-
enzyme form alpha
8.4 - 9
-
-
9
-
sharp, N- and C-terminally truncated enzyme (BS 71-400)
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5 - 10
-
-
6.5 - 9.5
-
activity increases with increasing pH, C52S and H65R mutant
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)
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
wild-type CBS is therminally activated at 55°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
-
Manually annotated by BRENDA team
-
cystathionine beta-synthase activities in wild-type individuals, and in hetero-, and homozygote cystathionine beta-synthase mutants, overview
Manually annotated by BRENDA team
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
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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
metabolism
malfunction
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
CBS_HUMAN
551
0
60587
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
250000
dynamic light scattering
45000
the protein is an active and stable dimer of 45 kDa subunits
1330000
-
multimer, gel filtration
235000
-
existence in multiple molecular forms of MW 50000-130000, 235000, 500000, gel filtration
250000
-
gel filtration
45000
-
molecular weight of the truncated protein lacking the C-terminal domain
48000
-
2 * 48000, proteolytically activated enzyme, derived from 4 * 68000 enzyme, SDS-PAGE
486000
-
octamer, gel filtration
50000 - 130000
-
existence in multiple molecular forms of MW 50000-130000, 235000, 500000, gel filtration
500000
-
existence in multiple molecular forms of MW 50000-130000, 235000, 500000, gel filtration
55000
-
x * 55000, SDS-PAGE
61000
-
4 * 61000
63000
65000
-
x * 65000, SDS-PAGE
68000
94000
-
gel filtration
additional information
-
high tendency for aggregation
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
2 * 45000 Da, truncated human CBS lacking 143 amino acids at the C-terminus
dimer
homodimer
-
truncated CBS, X-ray crystallography
homotetramer
multimer
-
wild-type enzyme and I435T mutant, gel filtration
octamer
-
wild-type enzyme and I435T mutant, gel filtration
oligomer
-
full length subunits for tetramers and higher oligomers
tetramer
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
-
trypsinolyis occurs initially at Lys30, Lys36, Lys39, then at Arg413 and transforms the tetrameric enzyme to a dimer of MW 85000 which is twice as active as the tetramer
sumoylation
-
CBS is modified by the small ubiquitin-like modifier-1 protein (SUMO-I) under both in vitro and in vivo conditions. Deletion analysis of CBS indicates that the C-terminal regulatory domain is required for interaction with proteins in the sumoylation machinery. Sumoylated CBS is present in the nucleus where it is associated with the nuclear scaffold
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
catalytic core, hanging drop vapor diffusion method
role of surface electrostatics. The kinetic stability of the catalytic and regulatory domains is significantly affected by the modulation of surface electrostatics through noticeable structural and energetic changes along their denaturation pathways. Surface electrostatics strongly affect SAM binding properties to those sites responsible for either enzyme activation or kinetic stabilization
structure of CBS with bound AdoMet. Binding of AdoMet triggers a conformational change in the Bateman module of the regulatory domain that favors its association with a Bateman module of the complementary subunit to form an antiparallel CBS module. In the presence of AdoMet, the autoinhibition exerted by the regulatory region is eliminated
truncated form
mutant lacking the S-adenosyl-L-methionine binding site and heme-free crystals, hanging drop vapor diffusion method
-
with heme and pyridoxal 5'-phosphate, hanging drop vapor diffusion method
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A114V
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
C272A
2fold lower heme content, 2fold lower specific activity, 2fold higher activity in the presence of S-adenosyl-L-methionine
C274S
2fold lower heme content, 2fold lower specific activity, 2fold higher activity in the presence of S-adenosyl-L-methionine
D198V
pathogenic mutation, no impact on specific activity and response to AdoMet
D234N
the mutation is associated with Venezuelan homocystinuria responsive to vitamin B6. The mutant shows 43% activity compared to the wild type enzyme
D444N
DELTAC143
a truncated human CBS lacking 143 amino acids at the C-terminus is used to study the inactivation of cystathionine beta-synthase by peroxynitrite
E144K
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
E201S
mutation leads to permanent activation of enzyme
G307S
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
I278T
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
I437T
mutation results in loss of S-adenosyl-L-methionine-dependent activation but exhibits basal activity that is comparable to that of wild-type enzyme expressed under the same conditions. Purified recombinant I435T shows a two to 3fold higher basal activity compared to wild-type enzyme but is unresponsive to the allosteric activator S-adenosyl-L-methionine
K523Sfs?18
enzymatic function of the variants is not impaired, increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
L540Q
enzymatic function of the variants is not impaired, increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
P427L
enzymatic function of the variants is not impaired. Mutant lacks activation by S-adenosyl-L-methionine, but binds it at low level and shows an increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
R125Q
R224A
the mutation decreases CBS activity by approximately 50%
R266K
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
R51A
the mutation decreases CBS activity by approximately 50%
S466L
S500L
about 71% of wild-type activity. Mutant lacks activation by S-adenosyl-L-methionine, but binds it at low level and shows an increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
T191M
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
T87N
the mutation is associated with Venezuelan homocystinuria nonresponsive to vitamin B6. The mutant shows 3.5% activity compared to the wild type enzyme
V449G
enzymatic function of the variants is not impaired, increase in the basal enzymatic activity in presence of pyridoxal 5'-phosphate
W409_G453del
naturally occuring mutant involved in CBS deficiency, three-dimensional CBS structure compared to the wild-type enzyme
A114V
A226T
A331V
-
mutation effects can be suppressed in a yeast assay by the deletion of the regulatory domain of the protein
C15S
-
mutagenesis does not affect catalysis or S-adenosyl-L-methionine activation but significantly reduces aggregation of the purified enzyme in vitro
C165Y
C431S
-
mutagenesis results in a constitutively activated form of CBS that can not be further activated by either S-adenosyl-L-methionine or thermal activation
C52A
-
reduced heme content, pyridoxal phosphate content comparable to wild-type enzyme, low catalytic activity
C52S
-
reduced heme content, pyridoxal phosphate content comparable to wild-type enzyme, low catalytic activity
D376N
-
mutant is not rescuable by any of the chemical chaperones
D444N
DELAT143
-
truncated human CBS lacking 143 amino acids at the C-terminus is purified from a recombinant expression system and is used for vibrational coherence spectroscopy
DELTAC
-
studies are carried out using a truncated protein lacking the C-terminal domain. kcat increases by a factor of 4 and the responsiveness to S-adenosyl-L-methionine is lost. The C-terminal domain is involved in the aggregation of the full-length protein, which exists as a mixture of tetramer and higher oligomers, while the 45 kDa truncated form lacking the C-terminal domain is a dimer
E144K
-
site-directed mutagenesis, inactive mutant
E176K
E302K
G116R
-
mutation in dimer interface of patients with homocystinurea
G148R
G259S
-
active site mutation in patients with homocystinurea
G305R
G307S
H67A
-
mutant is comparable to wild-type, specific activity and Km values for L-Ser, L-homocysteine comparable to wild-type
I152M
-
the mutation is associated with homocystinuria
I278T
I278T/T424N
-
mutant enzyme is inactive, although transgenic mouse line that expresses I278T/T424N possess the ability to rescue the neonatal lethality associated with homozygosity for the Cbs- allele
I435T
K102N
L539S
-
site-directed mutagenesis, inactive mutant, the mutant shows altered activity compared to the wild-type enzyme
N228K
N228S
P422L
P427L/S500L
-
the mutant is almost not activated by S-adenosyl-L-methionine
P78R/K102N
-
KM for L-serine is about 2fold higher than wild-type value. Mutant enzyme is insensitive to allosteric regulation and unresponsive to S-adenosyl-L-methionine
P88S
-
mutation in dimer interface of patients with homocystinurea
Q222X
-
mutagenesis studies reveal that Gln-222 is involved in interactions with substrates
Q526K
-
mutant is not rescuable by any of the chemical chaperones
R125Q
R125W
-
the mutation is associated with homocystinuria
R224H
-
mutation in the connecting loop between the N- and C-terminal domain between beta-strand 7 and alpha-helix 6, patients respond to vitamin B6 treatment
R266G
-
patient mutation , mutant protein shows instability and extensive degradation during thrombin treatment. A GST-R266G fusion protein does not exhibit any detectable activity unlike the GST-tagged wild-type CBS
R266K
R266M
R266X
-
mutagenesis studies reveal that Arg-266 is important to sense structural changes in heme-binding site
R336C
R336H
R369C
R439Q
R491C
-
the mutation is associated with homocystinuria
R58W
-
mutation in the heme binding site of patients with homocystinurea, reduced ability to bind heme
S352N
-
patients with this mutation are not vitamin B6 responsive
S466L
T191M
T223X
-
mutagenesis studies reveal that Tyr-223 is involved in interactions with substrates
T257M
-
active site mutation in patients with homocystinurea
T262M
-
expression of human mutant CBS proteins in Saccharomyces cerevisiae reveals that the disease causing mutation severely inhibits enzyme activity and cannot support growth of yeast on cysteine-free media. The osmolyte chemical chaperones glycerol, trimethylamine-N-oxide, dimethylsulfoxide, proline or sorbitol, when added to yeast media, allows growth on cysteine-free media and causes increased enzyme activity from I278T mutant protein. The increase in enzyme activity is associated with stabilization of the tetramer form of the enzyme. This effect is not specific to yeast, as addition of the chaperone glycerol results in increased I278T activity when the enzyme is produced either in Escherichia coli or in a coupled in vitro transcription/translation reaction. No stimulation of specific activity is observed when chaperones are added directly to purified I278T indicating that the presence of chemical chaperones is required during translation
T262R
-
site-directed mutagenesis, inactive mutant
T353M
T434N
-
the mutation is associated with homocystinuria
V180A
V354M
-
patients with this mutation are not vitamin B6 responsive
V371M
-
the mutation is associated with homocystinuria
W409_G453del
-
site-directed mutagenesis, inactive mutant
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
51.2
wild-type, melting temperature, regulatory domains
67
wild-type, melting temperature, catalytic domains
48
-
stable up to
55
-
melting point of wild type and S466L mutant
additional information
-
dissociation of tetrameric enzyme to dimeric form, initiated by proteolysis decreases thermostability
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
in the presence of 200 mM NaCl the kinetic stability of the regulatory domains is increased about 300fold while the stability of catalytic domains decreases about 5fold
2-mercaptoethanol stabilizes
-
binding of S-adenosyl-L-methionine stabilizes cystathionine beta-synthase against degradation. Under pathological conditions with reduced levels of S-adenosyl-L-methionine (human hepatocellular carcinoma), level of cystathionine beta-synthase is diminished. This decrease in cystathionine beta-synthase level correlates with reduced glutathione that is, in turn, associated with increased vulnerability to oxidative stress. Posttranslational regulation of cystathionine beta-synthase stability by S-adenosyl-L-methionine provides a mechanism for achieving coordinate changes in cellular methylation and antioxidant status that is observed in a number of disease states
-
high protein concentration stabilizes
-
lyophilization inactivates
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-15°C, 40% glycerol, 5 weeks stable
-
-20°C, 0.1 M Tris-HCl buffer, pH 7.5, 0.1 mM pyridoxal 5'-phosphate
-
-70°C
-
-80°C, potassium phosphate buffer, pH 6.5, 1 mM 2-mercaptoethanol, 3 years, no loss of activity
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
GST Trap FF column chromatography and Mono Q column chromatography
truncated human CBS lacking 143 amino acids at the C-terminus is purified as a fusion protein with glutathione S-transferase using the Escherichia coli expression vector pGEXCBSN. The protein is purified through affinity chromatography with glutathione sepharose and anion exchange chromatography. The glutathione Stransferase tag was cleaved by limited proteolysis using thrombin
CBSdeltaC143
-
full length enzyme exhibits a strong tendency toward aggregation during the course of purification as well as in the purified state
-
full length protein and truncated variant lacking 143 amino acid residues at the C-terminus
-
glutathione-Sepharose column chromatography
-
Ni-NTA column chromatography
-
recombinant GST-tagged wild-type and Co-subsituted CBS from Escherichia coli strain Rosetta 2 (DE3) by glutathione affinity and anion exchange chromatography
-
recombinant mutant 45CBS and wild-type CBS from Escherichia coli to homogeneity
-
two patient-derived forms S466L and I435T, 95% purity
-
using a glutathione sepharose column
-
wild type and truncated human cystathionine beta-synthase expressed in Escherichia coli
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli
full-length CBS and truncated enzyme containing residues 1-397 are expressed in Escherichia coli BL21 cells
genotyping of wild-type and mutant CBSs, determination of mutations in patients with homocystinuria due to CBS deficiency, overview
truncated human CBS lacking 143 amino acids at the C-terminus is expressed as a fusion protein with glutathione S-transferase in the Escherichia coli
a mutant form of the human cystathionine beta-synthase protein, I278T, is expressed in Saccharomyces cerevisiae
-
eight CBS mutants are expressed in Escherichia coli in the presence of chemical chaperones such as ethanol, dimethyl sulfoxide, or trimethylamine-N-oxide
-
expressed as a GST-fusion protein in Escherichia coli
-
expressed in Escherichia coli
-
expressed in Escherichia coli BL21(DE3) cells
-
expressed in Escherichia coli strain DH10B
-
expressed in heme-deficient strains of Saccharomyces cerevisiae and Escherichia coli
-
expression in Escherichia coli
-
expression in yeast or in Escherichia coli
-
expression of human mutant CBS proteins in Saccharomyces cerevisiae reveals that the disease causing mutation severely inhibits enzyme activity and cannot support growth of yeast on cysteine-free media. The osmolyte chemical chaperones glycerol, trimethylamine-N-oxide, dimethylsulfoxide, proline or sorbitol, when added to yeast media, allows growth on cysteine-free media and causes increased enzyme activity from I278T mutant protein. The increase in enzyme activity is associated with stabilization of the tetramer form of the enzyme. This effect is not specific to yeast, as addition of the chaperone glycerol results in increased I278T activity when the enzyme is produced either in Escherichia coli or in a coupled in vitro transcription/translation reaction. No stimulation of specific activity is observed when chaperones are added directly to purified I278T indicating that the presence of chemical chaperones is required during translation
-
expression of mutant 45CBS and wild-type CBS in Escherichia coli
-
expression of wild type and truncated human cystathionine beta-synthase enzyme in Escherichia coli
-
expression of wild-type and Co-subsituted CBS as GST-tagged enzymes in Escherichia coli strain Rosetta 2 (DE3)
-
fusion protein with glutathione S-transferase
-
in a recombinant expression system (pGEX4T1/hCBSDELTAC143) that produces a fusion protein with glutathione S-transferase
-
mutant enzymes K102N, P78R and P78R/K102N are expressed in Escherichia coli and purified as glutathione S-transferase fusion proteins using recombinant expression
-
the truncated human CBS enzyme consisting of residue 1-397 is expressed in the glutathione S-transferase fusion expression system
-
transgenic mice that contain the human cystathionine beta-synthase cDNA under control of the zinc-inducible metallothionein promoter (Tg-CBS). In the presence of zinc, Tg-CBS mice have a 2fold to 4fold increase in liver and kidney cystathionine beta-synthase activity compared with nontransgenic littermates
-
truncated form fused with glutathione S-transferase
-
truncated protein lacking the C-terminal domain is expressed
-
wild type enzyme is expressed in Mus musculus and mutant enzyme S466L is expressed in Saccharomyces cerevisiae strain WY35 and in Mus musculus
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
butyrate significantly increases CBS protein expression, butyrate-stimulated CBS expression is not changed by trichostatin A
-
decreased expression after exogenous addition alltrans-retinoic acid
-
expression level of CBS in 120 hepatocellular carcinoma specimens evaluated by RT-PCR is markedly lower than in surrounding non-cancerous liver. Reduced CBS expression is significantly correlated with high tumor stage. A survival analysis shows that a significantly shorter overall survival time is observed in patients with reduced CBS expression
-
protein level and activity increase with incubation time, upon stimulation, and similar to intracellular homocysteine, depending on intra- and extracellular homocysteine and glutathione concentrations
-
the enzyme is overexpressed in primary epithelial ovarian cancer and ovarian cancer cell lines
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
development of a LC-MS/MS and HPLC methods to simultaneously measure formation of thioethers and hydrogen sulfide from mixtures of cystathionine beta-synthase substrates
medicine
analysis
-
development of 7-azido-4-carbamoylmethylcoumarin as a modified fluorogenic probe for H2S detection with improved solubility in aqueous solutions
diagnostics
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Braunstein, A.E.; Goryachenkova, E.V.
The beta-replacement-specific pyridoxal-P-dependent lyases
Adv. Enzymol. Relat. Areas Mol. Biol.
56
1-89
1984
Gallus gallus, Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Kraus, J.P.; Rosenberg, L.E.
Cystathionine beta-synthase from human liver: improved purification scheme and additional characterization of the enzyme in crude and pure form
Arch. Biochem. Biophys.
222
44-52
1983
Homo sapiens
Manually annotated by BRENDA team
Kraus, J.; Packman, S.; Fowler, B.; Rosenberg, L.E.
Purification and properties of cystathionine beta-synthase from human liver
J. Biol. Chem.
253
6523-6528
1978
Homo sapiens
Manually annotated by BRENDA team
Ansell, P.R.J.; Tudball, N.
The existence of human liver cystathionine beta-synthase in multiple molecular forms
Biochim. Biophys. Acta
483
443-451
1977
Homo sapiens
Manually annotated by BRENDA team
Tudball, N.; Reed, M.A.
Purification and properties of cystathionine synthase from human liver
Biochem. Biophys. Res. Commun.
67
550-555
1975
Homo sapiens
Manually annotated by BRENDA team
Porter, P.N.; Grishaver, M.S.; Jones, O.W.
Characterization of human cystathionine beta-synthase. Evidence for the identity of human L-serine dehydratase and cystathionine beta-synthase
Biochim. Biophys. Acta
364
128-139
1974
Homo sapiens
Manually annotated by BRENDA team
Bukovska, G.; Kery, V.; Kraus, J.P.
Expression of human cystathionine beta-synthase in Escherichia coli: purification and characterization
Protein Expr. Purif.
5
442-448
1994
Homo sapiens
Manually annotated by BRENDA team
Taoka, S.; Ohja, S.; Shan, X.; Kruger, W.D.; Banerjee, R.
Evidence for heme-mediated redox regulation of human cystathionine beta-synthase activity
J. Biol. Chem.
273
25179-25184
1998
Homo sapiens
Manually annotated by BRENDA team
Kery, V.; Poneleit, L.; Meyer, J.D.; Manning, M.C.; Kraus, J.P.
Binding of pyridoxal 5'-phosphate to the heme protein human cystathionine beta-synthase
Biochemistry
38
2716-2724
1999
Homo sapiens
Manually annotated by BRENDA team
Kery, V.; Poneleit, L.; Kraus, J.P.
Trypsin cleavage of human cystathionine beta-synthase into an evolutionary conserved active core: structural and functional consequences
Arch. Biochem. Biophys.
355
222-232
1998
Homo sapiens
Manually annotated by BRENDA team
Gallagher, P.M.; Naughten, E.; Hanson, N.Q.; Schwichtenberg, K.; Bignell, M.; Yuan, M.; Ward, P.; Yap, S.; Whitehead, A.S.; Tsai, M.Y.
Characterization of mutations in the cystathionine beta-synthase gene in irish patients with homocystinuria
Mol. Genet. Metab.
65
298-302
1998
Homo sapiens
Manually annotated by BRENDA team
Janosik, M.; Meier, M.; Kery, V.; Oliveriusova, J.; Burkhard, P.; Kraus, J.P.
Crystallization and preliminary x-ray diffraction analysis of the active core of human recombinant cystathionine beta-synthase: an enzyme involved in vascular disease
Acta Crystallogr. Sect. D
D57
289-291
2001
Homo sapiens
Manually annotated by BRENDA team
Vadon-Le Goff, S.; Delaforge, M.; Boucher, J.L.; Janosik, M.; Kraus, J.P.; Mansuy, D.
Coordination chemistry of the heme in cystathionine beta-synthase: formation of iron(II)-isonitrile complexes
Biochem. Biophys. Res. Commun.
283
487-492
2001
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Taoka, S.; Widjaja, L.; Banerjee, R.
Assignment of enzymatic functions to specific regions of the PLP-dependent heme protein cystathionine beta-synthase
Biochemistry
38
13155-13161
1999
Homo sapiens
Manually annotated by BRENDA team
Taoka, S.; West, M.; Banerjee, R.
Characterization of the heme and pyridoxal phosphate cofactors of human cystathionine beta-synthase reveals nonequivalent active sites
Biochemistry
38
2738-2744
1999
Homo sapiens
Manually annotated by BRENDA team
Ojha, S.; Hwang, J.; Kabil, O.; Penner-Hahn, J.E.; Banerjee, R.
Characterization of the heme in human cystathionine beta-synthase by X-ray absorption and electron paramagnetic resonance spectroscopies
Biochemistry
39
10542-10547
2000
Homo sapiens
Manually annotated by BRENDA team
Janosik, M.; Kery, V.; Gaustadnes, M.; Maclean, K.N.; Kraus, J.P.
Regulation of human cystathionine beta-synthase by S-adenosyl-L-methionine: evidence for two catalytically active conformations involving an autoinhibitory domain in the C-terminal region
Biochemistry
40
10625-10633
2001
Homo sapiens
Manually annotated by BRENDA team
Taoka, S.; Lepore, B.W.; Kabil, O.; Ojha, S.; Ringe, D.; Banerjee, R.
Human cystathionine beta-synthase is a heme sensor protein. Evidence that the redox sensor is heme and not the vicinal cysteines in the CXXC motif seen in the crystal structure of the truncated enzyme
Biochemistry
41
10454-10461
2002
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team
Evande, R.; Blom, H.; Boers, G.H.; Banerjee, R.
Alleviation of intrasteric inhibition by the pathogenic activation domain mutation, D444N, in human cystathionine beta-synthase
Biochemistry
41
11832-11837
2002
Homo sapiens
Manually annotated by BRENDA team
Ojha, S.; Wu, J.; LoBrutto, R.; Banerjee, R.
Effects of heme ligand mutations including a pathogenic variant, H65R, on the properties of human cystathionine beta-synthase
Biochemistry
41
4649-4654
2002
Homo sapiens
Manually annotated by BRENDA team
Meier, M.; Oliveriusova, J.; Kraus, J.P.; Burkhard, P.
Structural insights into mutations of cystathionine beta-synthase
Biochim. Biophys. Acta
1647
206-213
2003
Homo sapiens
Manually annotated by BRENDA team
Banerjee, R.; Evande, R.; Kabil, O.; Ojha, S.; Taoka, S.
Reaction mechanism and regulation of cystathionine beta-synthase
Biochim. Biophys. Acta
1647
30-35
2003
Saccharomyces cerevisiae, Homo sapiens, Mammalia
Manually annotated by BRENDA team
Meier, M.; Janosik, M.; Kery, V.; Kraus, J.P.; Burkhard, P.
Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein
EMBO J.
20
3910-3916
2001
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team
Bruno, S.; Schiaretti, F.; Burkhard, P.; Kraus, J.P.; Janosik, M.; Mozzarelli, A.
Functional properties of the active core of human cystathionine beta-synthase crystals
J. Biol. Chem.
276
16-19
2001
Homo sapiens
Manually annotated by BRENDA team
Kabil, O.; Toaka, S.; LoBrutto, R.; Shoemaker, R.; Banerjee, R.
Pyridoxal phosphate binding sites are similar in human heme-dependent and yeast heme-independent cystathionine beta-synthases. Evidence from 31P NMR and pulsed EPR spectroscopy that heme and PLP cofactors are not proximal in the human enzyme
J. Biol. Chem.
276
19350-19355
2001
Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team
Oliveriusova, J.; Kery, V.; Maclean, K.N.; Kraus, J.P.
Deletion mutagenesis of human cystathionine beta-synthase. Impact on activity, oligomeric status, and S-adenosylmethionine regulation
J. Biol. Chem.
277
48386-48394
2002
Homo sapiens
Manually annotated by BRENDA team
Zou, C.G.; Banerjee, R.
Tumor necrosis factor-a-induced targeted proteolysis of cystathionine beta-xynthase modulates redox homeostasis
J. Biol. Chem.
278
16802-16808
2003
Homo sapiens
Manually annotated by BRENDA team
Miles, E.W.; Kraus, J.P.
Cystathionine {beta}-synthase: structure, function, regulation and location of homocystinuria-causing mutations
J. Biol. Chem.
279
29871-29874
2004
Saccharomyces cerevisiae, Trypanosoma cruzi, Homo sapiens (P35520)
Manually annotated by BRENDA team
Taoka, S.; Banerjee, R.
Characterization of NO binding to human cystathionine beta-synthase: possible implications of the effects of CO and NO binding to the human enzyme
J. Inorg. Biochem.
87
245-251
2001
Homo sapiens
Manually annotated by BRENDA team
Taoka, S.; Green, E.L.; Loehr, T.M.; Banerjee, R.
Mercuric chloride-induced spin or ligation state changes in ferric or ferrous human cystathionine beta-synthase inhibit enzyme activity
J. Inorg. Biochem.
87
253-259
2001
Homo sapiens
Manually annotated by BRENDA team
Shen, W.; McGath, M.K.; Evande, R.; Berkowitz, D.B.
A continuous spectrophotometric assay for human cystathionine beta-synthase
Anal. Biochem.
342
103-110
2005
Homo sapiens
Manually annotated by BRENDA team
Ichinohe, A.; Kanaumi, T.; Takashima, S.; Enokido, Y.; Nagai, Y.; Kimura, H.
Cystathionine beta-synthase is enriched in the brains of Down's patients
Biochem. Biophys. Res. Commun.
338
1547-1550
2005
Homo sapiens
Manually annotated by BRENDA team
Pazicni, S.; Lukat-Rodgers, G.S.; Oliveriusova, J.; Rees, K.A.; Parks, R.B.; Clark, R.W.; Rodgers, K.R.; Kraus, J.P.; Burstyn, J.N.
The redox behavior of the heme in cystathionine beta-synthase is sensitive to pH
Biochemistry
43
14684-14695
2004
Homo sapiens
Manually annotated by BRENDA team
Wang, L.; Jhee, K.H.; Hua, X.; DiBello, P.M.; Jacobsen, D.W.; Kruger, W.D.
Modulation of cystathionine beta-synthase level regulates total serum homocysteine in mice
Circ. Res.
94
1318-1324
2004
Homo sapiens
Manually annotated by BRENDA team
Wang, L.; Chen, X.; Tang, B.; Hua, X.; Klein-Szanto, A.; Kruger, W.D.
Expression of mutant human cystathionine beta-synthase rescues neonatal lethality but not homocystinuria in a mouse model
Hum. Mol. Genet.
14
2201-2208
2005
Homo sapiens
Manually annotated by BRENDA team
Chen, X.; Jhee, K.H.; Kruger, W.D.
Production of the neuromodulator H2S by cystathionine beta-synthase via the condensation of cysteine and homocysteine
J. Biol. Chem.
279
52082-52086
2004
Homo sapiens
Manually annotated by BRENDA team
de Lucca, M.; Casique, L.
Characterization of cystathionine b-synthase gene mutations in homocystinuric Venezuelan patients: identification of one novel mutation in exon 6
Mol. Genet. Metab.
81
209-215
2004
Homo sapiens
Manually annotated by BRENDA team
Vitvitsky, V.; Prudova, A.; Stabler, S.; Dayal, S.; Lentz, S.R.; Banerjee, R.
Testosterone regulation of renal cystathionine beta-synthase: implications for sex-dependent differences in plasma homocysteine levels
Am. J. Physiol. Renal Physiol.
293
F594-F600
2007
Cavia porcellus, Oryctolagus cuniculus, Homo sapiens, Mesocricetus auratus, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Frank, N.; Kent, J.O.; Meier, M.; Kraus, J.P.
Purification and characterization of the wild type and truncated human cystathionine beta-synthase enzymes expressed in E. coli
Arch. Biochem. Biophys.
470
64-72
2007
Homo sapiens
Manually annotated by BRENDA team
Frank, N.; Kery, V.; Maclean, K.N.; Kraus, J.P.
Solvent-accessible cysteines in human cystathionine beta-synthase: crucial role of cysteine 431 in S-adenosyl-L-methionine binding
Biochemistry
45
11021-11029
2006
Homo sapiens
Manually annotated by BRENDA team
Kabil, O.; Zhou, Y.; Banerjee, R.
Human cystathionine beta-synthase is a target for sumoylation
Biochemistry
45
13528-13536
2006
Homo sapiens
Manually annotated by BRENDA team
Cherney, M.M.; Pazicni, S.; Frank, N.; Marvin, K.A.; Kraus, J.P.; Burstyn, J.N.
Ferrous human cystathionine beta-synthase loses activity during enzyme assay due to a ligand switch process
Biochemistry
46
13199-13210
2007
Homo sapiens
Manually annotated by BRENDA team
Sen, S.; Banerjee, R.
A pathogenic linked mutation in the catalytic core of human cystathionine beta-synthase disrupts allosteric regulation and allows kinetic characterization of a full-length dimer
Biochemistry
46
4110-4116
2007
Homo sapiens
Manually annotated by BRENDA team
Linnebank, M.; Semmler, A.; Kleijer, W.J.; van der Sterre, M.L.; Gaertner, J.; Fliessbach, K.; Sokolowski, P.; Koehler, W.; Schlegel, U.; Klockgether, T.; Wanders, R.J.; Schmidt, S.; Wuellner, U.; Kemp, S.
The cystathionine beta-synthase variant c.844_845ins68 protects against CNS demyelination in X-linked adrenoleukodystrophy
Hum. Mutat.
27
1063-1064
2006
Homo sapiens
Manually annotated by BRENDA team
Chen, X.; Wang, L.; Fazlieva, R.; Kruger, W.D.
Contrasting behaviors of mutant cystathionine beta-synthase enzymes associated with pyridoxine response
Hum. Mutat.
27
474-482
2006
Homo sapiens
Manually annotated by BRENDA team
Vyletal, P.; Sokolova, J.; Cooper, D.N.; Kraus, J.P.; Krawczak, M.; Pepe, G.; Rickards, O.; Koch, H.G.; Linnebank, M.; Kluijtmans, L.A.; Blom, H.J.; Boers, G.H.; Gaustadnes, M.; Skovby, F.; Wilcken, B.; Wilcken, D.E.; Andria, G.; Sebastio, G.; Naughten, E.R.; Yap, S.; Ohura, T.; Pronicka, E.; Laszlo, A.; Ko, K.o.z.
Diversity of cystathionine beta-synthase haplotypes bearing the most common homocystinuria mutation c.833T>C: a possible role for gene conversion
Hum. Mutat.
28
255-264
2007
Homo sapiens
Manually annotated by BRENDA team
Puranik, M.; Weeks, C.L.; Lahaye, D.; Kabil, O.; Taoka, S.; Nielsen, S.B.; Groves, J.T.; Banerjee, R.; Spiro, T.G.
Dynamics of carbon monoxide binding to cystathionine beta-synthase
J. Biol. Chem.
281
13433-13438
2006
Homo sapiens (P35520)
Manually annotated by BRENDA team
Yamanishi, M.; Kabil, O.; Sen, S.; Banerjee, R.
Structural insights into pathogenic mutations in heme-dependent cystathionine-beta-synthase
J. Inorg. Biochem.
100
1988-1995
2006
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team
Singh, L.R.; Chen, X.; Kozich, V.; Kruger, W.D.
Chemical chaperone rescue of mutant human cystathionine beta-synthase
Mol. Genet. Metab.
91
335-342
2007
Homo sapiens
Manually annotated by BRENDA team
Singh, S.; Madzelan, P.; Banerjee, R.
Properties of an unusual heme cofactor in PLP-dependent cystathionine beta-synthase
Nat. Prod. Rep.
24
631-639
2007
Homo sapiens (P35520)
Manually annotated by BRENDA team
Prudova, A.; Bauman, Z.; Braun, A.; Vitvitsky, V.; Lu, S.C.; Banerjee, R.
S-adenosylmethionine stabilizes cystathionine beta-synthase and modulates redox capacity
Proc. Natl. Acad. Sci. USA
103
6489-6494
2006
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Summers, C.M.; Hammons, A.L.; Mitchell, L.E.; Woodside, J.V.; Yarnell, J.W.; Young, I.S.; Evans, A.; Whitehead, A.S.
Influence of the cystathionine beta-synthase 844ins68 and methylenetetrahydrofolate reductase 677C>T polymorphisms on folate and homocysteine concentrations
Eur. J. Hum. Genet.
16
1010-1013
2008
Homo sapiens
Manually annotated by BRENDA team
Ott, N.; Geddert, H.; Sarbia, M.
Polymorphisms in methionine synthase (A2756G) and cystathionine beta-synthase (844ins68) and susceptibility to carcinomas of the upper gastrointestinal tract
J. Cancer Res. Clin. Oncol.
134
405-410
2008
Homo sapiens
Manually annotated by BRENDA team
Carballal, S.; Madzelan, P.; Zinola, C.F.; Grana, M.; Radi, R.; Banerjee, R.; Alvarez, B.
Dioxygen reactivity and heme redox potential of truncated human cystathionine beta-synthase
Biochemistry
47
3194-3201
2008
Homo sapiens
Manually annotated by BRENDA team
Ozaki, S.; Inada, A.; Sada, K.
Modulation of cystathionine beta-synthase activity by the Arg-51 and Arg-224 mutations
Biosci. Biotechnol. Biochem.
72
2318-2323
2008
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team
Ozaki, S.; Doi, M.; Migita, C.T.
Modulation of cystathionine beta-synthase activity by altering heme environment
Chem. Lett.
37
208-209
2008
Homo sapiens
-
Manually annotated by BRENDA team
Jakubowski, H.; Boers, G.H.; Strauss, K.A.
Mutations in cystathionine beta-synthase or methylenetetrahydrofolate reductase gene increase N-homocysteinylated protein levels in humans
FASEB J.
22
4071-4076
2008
Homo sapiens
Manually annotated by BRENDA team
Gupta, S.; Wang, L.; Hua, X.; Krijt, J.; Kozich, V.; Kruger, W.D.
Cystathionine beta-synthase p.S466L mutation causes hyperhomocysteinemia in mice
Hum. Mutat.
29
1048-1054
2008
Homo sapiens
Manually annotated by BRENDA team
Majtan, T.; Singh, L.R.; Wang, L.; Kruger, W.D.; Kraus, J.P.
Active cystathionine beta-synthase can be expressed in heme-free systems in the presence of metal-substituted porphyrins or a chemical chaperone
J. Biol. Chem.
283
34588-34595
2008
Homo sapiens
Manually annotated by BRENDA team
Belew, M.S.; Quazi, F.I.; Willmore, W.G.; Aitken, S.M.
Kinetic characterization of recombinant human cystathionine beta-synthase purified from E. coli
Protein Expr. Purif.
64
139-145
2009
Homo sapiens
Manually annotated by BRENDA team
Cao, Q.; Zhang, L.; Yang, G.; Xu, C.; Wang, R.
Butyrate-stimulated H2S production in colon cancer cells
Antioxid. Redox Signal.
12
1101-1109
2010
Homo sapiens
Manually annotated by BRENDA team
Celano, L.; Gil, M.; Carballal, S.; Duran, R.; Denicola, A.; Banerjee, R.; Alvarez, B.
Inactivation of cystathionine beta-synthase with peroxynitrite
Arch. Biochem. Biophys.
491
96-105
2009
Homo sapiens (P35520)
Manually annotated by BRENDA team
Weeks, C.L.; Singh, S.; Madzelan, P.; Banerjee, R.; Spiro, T.G.
Heme regulation of human cystathionine beta-synthase activity: insights from fluorescence and Raman spectroscopy
J. Am. Chem. Soc.
131
12809-12816
2009
Homo sapiens
Manually annotated by BRENDA team
Singh, L.; Kruger, W.
Functional rescue of mutant human cystathionine -synthase by manipulation of Hsp26 and Hsp70 levels in Saccharomyces cerevisiae
J. Biol. Chem.
284
4238-4245
2009
Homo sapiens
Manually annotated by BRENDA team
Majtan, T.; Liu, L.; Carpenter, J.F.; Kraus, J.P.
Rescue of cystathionine beta-synthase (CBS) mutants with chemical chaperones: purification and characterization of eight CBS mutant enzymes
J. Biol. Chem.
285
15866-15873
2010
Homo sapiens
Manually annotated by BRENDA team
Xu, Y.Y.; Guan, D.Y.; Yang, M.; Wang, H.; Shen, Z.H.
All-trans-retinoic acid intensifies endoplasmic reticulum stress in N-acetylglucosaminyltransferase V repressed human hepatocarcinoma cells by perturbing homocysteine metabolism
J. Cell. Biochem.
109
468-477
2010
Homo sapiens
Manually annotated by BRENDA team
Singh, S.; Madzelan, P.; Stasser, J.; Weeks, C.L.; Becker, D.; Spiro, T.G.; Penner-Hahn, J.; Banerjee, R.
Modulation of the heme electronic structure and cystathionine beta-synthase activity by second coordination sphere ligands: The role of heme ligand switching in redox regulation
J. Inorg. Biochem.
103
689-697
2009
Homo sapiens
Manually annotated by BRENDA team
Karunakaran, V.; Benabbas, A.; Sun, Y.; Zhang, Z.; Singh, S.; Banerjee, R.; Champion, P.M.
Investigations of low-frequency vibrational dynamics and ligand binding kinetics of cystathionine beta-synthase
J. Phys. Chem. B
114
3294-3306
2010
Homo sapiens
Manually annotated by BRENDA team
Kim, J.; Hong, S.J.; Park, J.H.; Park, S.Y.; Kim, S.W.; Cho, E.Y.; Do, I.G.; Joh, J.W.; Kim, D.S.
Expression of cystathionine beta-synthase is downregulated in hepatocellular carcinoma and associated with poor prognosis
Oncol. Rep.
21
1449-1454
2009
Homo sapiens
Manually annotated by BRENDA team
Ozaki, S.; Sakaguchi, C.; Nakahara, A.; Yoshiya, M.
Mutagenesis studies of human cystathionine beta-synthase: residues important for heme binding and substrate interactions
Protein Pept. Lett.
17
351-355
2010
Homo sapiens
Manually annotated by BRENDA team
Majtan, T.; Freeman, K.M.; Smith, A.T.; Burstyn, J.N.; Kraus, J.P.
Purification and characterization of cystathionine beta-synthase bearing a cobalt protoporphyrin
Arch. Biochem. Biophys.
508
25-30
2011
Homo sapiens
Manually annotated by BRENDA team
Ishikawa, K.; Mino, K.; Nakamura, T.
New function and application of the cysteine synthase from archaea
Biochem. Eng. J.
48
315-322
2010
Saccharomyces cerevisiae (P32582), Homo sapiens (P35520), Aeropyrum pernix (Q9YCN5)
-
Manually annotated by BRENDA team
Hnizda, A.; Spiwok, V.; Jurga, V.; Kozich, V.; Kodicek, M.; Kraus, J.P.
Cross-talk between the catalytic core and the regulatory domain in cystathionine beta-synthase: study by differential covalent labeling and computational modeling
Biochemistry
49
10526-10534
2010
Homo sapiens
Manually annotated by BRENDA team
Jensen, K.K.; Geoghagen, N.S.; Jin, L.; Holt, T.G.; Luo, Q.; Malkowitz, L.; Ni, W.; Quan, S.; Waters, M.G.; Zhang, A.; Zhou, H.H.; Cheng, K.; Luo, M.J.
Pharmacological activation and genetic manipulation of cystathionine beta-synthase alter circulating levels of homocysteine and hydrogen sulfide in mice
Eur. J. Pharmacol.
650
86-93
2011
Homo sapiens, Mus musculus, Rattus norvegicus
Manually annotated by BRENDA team
Kozich, V.; Sokolova, J.; Klatovska, V.; Krijt, J.; Janosik, M.; Jelinek, K.; Kraus, J.P.
Cystathionine beta-synthase mutations: effect of mutation topology on folding and activity
Hum. Mutat.
31
809-819
2010
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team
Smith, A.T.; Majtan, T.; Freeman, K.M.; Su, Y.; Kraus, J.P.; Burstyn, J.N.
Cobalt cystathionine beta-synthase: a cobalt-substituted heme protein with a unique thiolate ligation motif
Inorg. Chem.
50
4417-4427
2011
Homo sapiens
Manually annotated by BRENDA team
Kopecka, J.; Krijt, J.; Rakova, K.; Kozich, V.
Restoring assembly and activity of cystathionine beta-synthase mutants by ligands and chemical chaperones
J. Inherit. Metab. Dis.
34
39-48
2011
Homo sapiens
Manually annotated by BRENDA team
Krijt, J.; Kopecka, J.; Hnizda, A.; Moat, S.; Kluijtmans, L.A.; Mayne, P.; Kozich, V.
Determination of cystathionine beta-synthase activity in human plasma by LC-MS/MS: potential use in diagnosis of CBS deficiency
J. Inherit. Metab. Dis.
34
49-55
2011
Homo sapiens
Manually annotated by BRENDA team
Albertini, E.; Koziel, R.; Duerr, A.; Neuhaus, M.; Jansen-Duerr, P.
Cystathionine beta synthase modulates senescence of human endothelial cells
Aging
4
664-673
2012
Homo sapiens
Manually annotated by BRENDA team
Katko, M.; Zavaczki, E.; Jeney, V.; Paragh, G.; Balla, J.; Varga, Z.
Homocysteine metabolism in peripheral blood mononuclear cells: evidence for cystathionine beta-synthase activity in resting state
Amino Acids
43
317-326
2012
Homo sapiens
Manually annotated by BRENDA team
Casique, L.; Kabil, O.; Banerjee, R.; Martinez, J.C.; De Lucca, M.
Characterization of two pathogenic mutations in cystathionine beta-synthase: different intracellular locations for wild-type and mutant proteins
Gene
531
117-124
2013
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team
Hnizda, A.; Jurga, V.; Rakova, K.; Kozich, V.
Cystathionine beta-synthase mutants exhibit changes in protein unfolding: conformational analysis of misfolded variants in crude cell extracts
J. Inherit. Metab. Dis.
35
469-477
2012
Homo sapiens
Manually annotated by BRENDA team
Mendes, M.I.; Colaco, H.G.; Smith, D.E.; Ramos, R.J.; Pop, A.; van Dooren, S.J.; Tavares de Almeida, I.; Kluijtmans, L.A.; Janssen, M.C.; Rivera, I.; Salomons, G.S.; Leandro, P.; Blom, H.J.
Reduced response of cystathionine beta-synthase (CBS) to S-adenosylmethionine (SAM): Identification and functional analysis of CBS gene mutations in homocystinuria patients
J. Inherit. Metab. Dis.
37
245-254
2014
Homo sapiens
Manually annotated by BRENDA team
Bhattacharyya, S.; Saha, S.; Giri, K.; Lanza, I.R.; Nair, K.S.; Jennings, N.B.; Rodriguez-Aguayo, C.; Lopez-Berestein, G.; Basal, E.; Weaver, A.L.; Visscher, D.W.; Cliby, W.; Sood, A.K.; Bhattacharya, R.; Mukherjee, P.
Cystathionine beta-synthase (CBS) contributes to advanced ovarian cancer progression and drug resistance
PLoS ONE
8
e79167
2013
Homo sapiens
Manually annotated by BRENDA team
Majtan, T.; Krijt, J.; Sokolova, J.; Krizkova, M.; Ralat, M.A.; Kent, J.; Gregory, J.F.; Kozich, V.; Kraus, J.P.
Biogenesis of hydrogen sulfide and thioethers by cystathionine beta-synthase
Antioxid. Redox Signal.
28
311-323
2018
Homo sapiens (P35520)
Manually annotated by BRENDA team
Pey, A.L.; Majtan, T.; Kraus, J.P.
The role of surface electrostatics on the stability, function and regulation of human cystathionine beta-synthase, a complex multidomain and oligomeric protein
Biochim. Biophys. Acta
1844
1453-1462
2014
Homo sapiens (P35520)
Manually annotated by BRENDA team
Majtan, T.; Pey, A.L.; Kraus, J.P.
Kinetic stability of cystathionine beta-synthase can be modulated by structural analogs of S-adenosylmethionine Potential approach to pharmacological chaperone therapy for homocystinuria
Biochimie
126
6-13
2016
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team
Thorson, M.; Van Wagoner, R.; Harper, M.; Ireland, C.; Majtan, T.; Kraus, J.; Barrios, A.
Marine natural products as inhibitors of cystathionine beta-synthase activity
Bioorg. Med. Chem. Lett.
25
1070-1072
2015
Homo sapiens
Manually annotated by BRENDA team
Saha, S.; Chakraborty, P.K.; Xiong, X.; Dwivedi, S.K.; Mustafi, S.B.; Leigh, N.R.; Ramchandran, R.; Mukherjee, P.; Bhattacharya, R.
Cystathionine beta-synthase regulates endothelial function via protein S-sulfhydration
FASEB J.
30
441-456
2016
Homo sapiens
Manually annotated by BRENDA team
Chakraborty, P.K.; Murphy, B.; Mustafi, S.B.; Dey, A.; Xiong, X.; Rao, G.; Naz, S.; Zhang, M.; Yang, D.; Dhanasekaran, D.N.; Bhattacharya, R.; Mukherjee, P.
Cystathionine beta-synthase regulates mitochondrial morphogenesis in ovarian cancer
FASEB J.
32
4145-4157
2018
Homo sapiens
Manually annotated by BRENDA team
Pey, A.L.; Martinez-Cruz, L.A.; Kraus, J.P.; Majtan, T.
Oligomeric status of human cystathionine beta-synthase modulates AdoMet binding
FEBS Lett.
590
4461-4471
2016
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team
Sen, S.; Kawahara, B.; Gupta, D.; Tsai, R.; Khachatryan, M.; Roy-Chowdhuri, S.; Bose, S.; Yoon, A.; Faull, K.; Farias-Eisner, R.; Chaudhuri, G.
Role of cystathionine beta-synthase in human breast cancer
Free Radic. Biol. Med.
86
228-238
2015
Homo sapiens
Manually annotated by BRENDA team
Mendes, M.I.; Santos, A.S.; Smith, D.E.; Lino, P.R.; Colaco, H.G.; de Almeida, I.T.; Vicente, J.B.; Salomons, G.S.; Rivera, I.; Blom, H.J.; Leandro, P.
Insights into the regulatory domain of cystathionine beta-synthase characterization of six variant proteins
Hum. Mutat.
35
1195-1202
2014
Homo sapiens (P35520)
Manually annotated by BRENDA team
Vicente, J.B.; Colaco, H.G.; Sarti, P.; Leandro, P.; Giuffre, A.
S-Adenosyl-L-methionine modulates CO and NO* binding to the human H2S-generating enzyme cystathionine beta-synthase
J. Biol. Chem.
291
572-581
2016
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team
Carballal, S.; Cuevasanta, E.; Yadav, P.K.; Gherasim, C.; Ballou, D.P.; Alvarez, B.; Banerjee, R.
Kinetics of nitrite reduction and peroxynitrite formation by ferrous heme in human cystathionine beta-synthase
J. Biol. Chem.
291
8004-8013
2016
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team
Niu, W.; Wang, J.; Qian, J.; Wang, M.; Wu, P.; Chen, F.; Yan, S.
Allosteric control of human cystathionine beta-synthase activity by a redox active disulfide bond
J. Biol. Chem.
293
2523-2533
2018
Homo sapiens
Manually annotated by BRENDA team
Chakraborty, P.K.; Xiong, X.; Mustafi, S.B.; Saha, S.; Dhanasekaran, D.; Mandal, N.A.; McMeekin, S.; Bhattacharya, R.; Mukherjee, P.
Role of cystathionine beta synthase in lipid metabolism in ovarian cancer
Oncotarget
6
37367-37384
2015
Homo sapiens
Manually annotated by BRENDA team
Majtan, T.; Pey, A.L.; Fernandez, R.; Fernandez, J.A.; Martinez-Cruz, L.A.; Kraus, J.P.
Domain organization, catalysis and regulation of eukaryotic cystathionine beta-synthases
PLoS ONE
9
e105290
2014
Saccharomyces cerevisiae, Drosophila melanogaster, Homo sapiens
Manually annotated by BRENDA team
Ereno-Orbea, J.; Majtan, T.; Oyenarte, I.; Kraus, J.P.; Martinez-Cruz, L.A.
Structural insight into the molecular mechanism of allosteric activation of human cystathionine beta-synthase by S-adenosylmethionine
Proc. Natl. Acad. Sci. USA
111
E3845-E3852
2014
Homo sapiens (P35520), Homo sapiens
Manually annotated by BRENDA team