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
Biosynthesis of antibiotics
-
-
Cysteine and methionine metabolism
-
-
Glycine, serine and threonine metabolism
-
-
homocysteine and cysteine interconversion
-
-
L-cysteine biosynthesis III (from L-homocysteine)
-
-
L-cysteine biosynthesis VI (from L-methionine)
-
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Metabolic pathways
-
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cysteine metabolism
-
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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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Manually annotated by BRENDA team
vervet monkey
-
-
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
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 71400 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
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2fold decrease in enzyme activity due to altered oxidation state of the heme
ellagic acid
Hexachlorophene
Hg2+
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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
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regulatory role
pyridoxal 5'-phosphate
S-adenosyl-L-methionine
S-adenosylhomocysteine
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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
7.97
L-Ser
Saccharomyces cerevisiae
-
-
0.052 - 45
L-serine
additional information
additional information
Saccharomyces cerevisiae
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the kcat for the generation of H2S by cystathionine beta-synthase of 55/s at 37C, 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
585
6.3 - 80
L-homocysteine
305
0.031 - 25
L-serine
95
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.6
CO
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37C under anaerobic conditions
2.3
cyanide
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37C
2.1
L-homocysteine
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recombinant 6-His-tagged enzyme, in 50 mM Tris (pH 8.6), at 25C
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 25C
0.68
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without pyridoxal 5'-phosphate, without S-adenosyl-L-methionine, mutant R266M
1.3
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full-length ferrous mutant enzyme R224A, at 37C and pH 8; full-length ferrous mutant enzyme R51A, at 37C 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 37C and pH 8; full-length ferric mutant enzyme R51A, at 37C 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 37C and pH 8
3.17
-
recombinant 6-His-tagged enzyme after purification, in 50 mM Tris (pH 8.6), at 25C
3.5
-
-
3.6
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without pyridoxal 5'-phosphate, without S-adenosyl-L-methionine, wild-type
3.8
-
truncated ferrous mutant enzyme R224A, at 37C 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 37C 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 37C and pH 8
8
-
truncated ferrous wild type enzyme, at 37C and pH 8
10.3
-
full-length ferric wild type enzyme, at 37C and pH 8
105.2
-
purified recombinant CoCBS, pH 8.6, 37C
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
-
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 55C
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
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
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
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
hanging drop vapour diffusion method, 100 mM phosphate-acetate pH 4.2, 200 mM NaCl and 20% (w/v) PEG 8000
-
enzyme free or in complex with a carbanion and an aminoacrylate intermediate, X-ray diffraction structure determination and analysis at 1.70 A and 1.55 A resolution, respectively
catalytic core, hanging drop vapor diffusion method
-
mutant lacking the S-adenosyl-L-methionine binding site and heme-free crystals, hanging drop vapor diffusion method
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truncated form
-
with heme and pyridoxal 5'-phosphate, hanging drop vapor diffusion method
-
crystal structures of both mercury- and iron-bound TA0289 (1.52.0 A resolution) reveals a dimeric protein whose intersubunit contacts are formed exclusively by the alpha-helices of two cystathionine beta-synthase subdomains, whereas the C-terminal domain has a classical Zn ribbon planar architecture
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nanodropletvapor diffusion method, crystal structure of a tandem cystathionine-beta-synthase domain protein (TM0935) from Thermotoga maritima at 1.87 A resolution
-
TEMPERATURE STABILITY
ORGANISM
UNIPROT