Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Transsulfuration depends on heme in addition to pyridoxal 5'-phosphate. Cystathionine beta-synthase is a heme protein.
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CBS binds both heme b and PLP with 1:1 stoichiometry
"1 mol of the 63-kDa CBS subunit binds 1 mol of each (heme and PLP)"
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Heme is required for PLP binding
"The presence of heme is required for PLP binding, and the amount of PLP bound is limited by the heme content"
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Heme saturation correlates with specific activity
"delta-Aminolevulinate supplementation during bacterial growth increases both the heme saturation and the specific activity of the homogeneous enzyme more than 3-fold"
Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein.
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Crystal structure of truncated CBS determined
"Here we present the X-ray crystal structure of a truncated form of the enzyme"
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CBS shares fold with O-acetylserine sulfhydrylase
"CBS shares the same fold with O-acetylserine sulfhydrylase but it contains an additional N-terminal heme binding site"
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Contains N-terminal heme binding domain
"CBS shares the same fold with O-acetylserine sulfhydrylase but it contains an additional N-terminal heme binding site"
Production of the neuromodulator H2S by cystathionine beta-synthase via the condensation of cysteine and homocysteine.
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CBS produces H2S via cysteine+homocysteine beta-replacement
"the CBS enzyme can efficiently produce H2S via a beta-replacement reaction in which cysteine is condensed with homocysteine to form cystathionine and H2S"
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H2S production 50x more efficient than cysteine hydrolysis
"The production of H2S by this reaction is at least 50 times more efficient than that produced by hydrolysis of cysteine alone via beta-elimination"
Towards a proteome-scale map of the human protein-protein interaction network.
Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins.
Human cystathionine beta-synthase is a target for sumoylation.
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CBS interacts with Ubc9, PIAS1, PIAS3, Pc2, RanBPM
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CBS is sumoylated at Lys-211
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Sumoylated CBS localizes to nucleus
Modulation of cystathionine beta-synthase activity by the Arg-51 and Arg-224 mutations.
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Arg-51 and Arg-224 interact with heme propionates
"we performed mutagenesis of Arg-51 and Arg-224, which have hydrogen-bonding interactions with propionate side chains of the prosthetic group"
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Mutations decrease CBS activity by approximately 50%
"the arginine mutations decrease CBS activity by approximately 50%"
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Structural changes at heme transmitted to PLP site
"The results indicate that structural changes in the heme vicinity are transmitted to PLP existing 20 A away from heme"
Kinetic characterization of recombinant human cystathionine beta-synthase purified from E. coli.
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Detailed kinetic parameters for CBS-catalyzed reactions
"the steady-state kinetic parameters of hCBS, via global analysis, and revealed previously unreported substrate inhibition by L-Hcys"
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Substrate inhibition by L-homocysteine (Ki = 2.1 mM)
"revealed previously unreported substrate inhibition by L-Hcys (K(i)(L-HCYS) = 2.1 +/- 0.2 mM)"
Shifted Transversal Design smart-pooling for high coverage interactome mapping.
Novel associations of CPS1, MUT, NOX4, and DPEP1 with plasma homocysteine in a healthy population: a genome-wide evaluation of 13 974 participants in the Women's Genome Health Study.
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GWAS confirms CBS association with homocysteine levels
"we confirm association with MTHFR (1p36.22; rs1801133; P=8.1 x 10(-35)) and CBS (21q22.3; rs6586282; P=3.2 x 10(-10))"
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CBS catalyzes first step of transsulfuration
"CBS catalyses the first step in the transsulfuration pathway of homocysteine catabolism"
Protein interactome reveals converging molecular pathways among autism disorders.
A directed protein interaction network for investigating intracellular signal transduction.
Human cystathionine β-synthase (CBS) contains two classes of binding sites for S-adenosylmethionine (SAM): complex regulation of CBS activity and stability by SAM.
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Two sets of SAM-binding sites identified
"We found two sets of SAM-binding sites in the C-terminal regulatory domain with different structural and energetic features"
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High-affinity sites for kinetic stabilization
"a high affinity set of two sites, probably involved in kinetic stabilization of the regulatory domain"
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Low-affinity sites for enzyme activation
"a low affinity set of four sites, which are involved in the enzyme activation"
Characterization of two pathogenic mutations in cystathionine beta-synthase: different intracellular locations for wild-type and mutant proteins.
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Wild-type CBS homogeneously distributed in cytoplasm
"the wild-type protein was homogeneously distributed inside the cell"
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Mutants show altered localization (punctate)
"While the T87N mutant exhibited a punctate appearance, the wild-type protein was homogeneously distributed inside the cell"
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Activity assays confirm CBS function
"Residual activities obtained for the mutant proteins were 3.5% T87N and 43% D234N"
Nitrite reductase activity and inhibition of H₂S biogenesis by human cystathionine ß-synthase.
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CBS has nitrite reductase activity via heme
"In this study, we have identified human cystathionine ß-synthase (CBS) as a new player in nitrite reduction"
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NO binding to heme inhibits CBS activity
"Binding of carbon monoxide (CO) or NO to the FeII-CBS heme inhibits enzyme activity"
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FeII-NO CBS inhibits H2S production by ~90%
"Formation of FeII-NO CBS was correlated with ∼90% inhibition of H2S production in the presence of cysteine+homocysteine"
NO* binds human cystathionine β-synthase quickly and tightly.
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NO binds tightly to ferrous CBS heme (Kd less than 0.23 microM)
"We found that NO(•) binds tightly to the ferrous CBS heme, with an apparent Kd ≤ 0.23 μm"
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Quick binding (kon approx. 8x10^3 M-1 s-1)
"at 25 °C, NO(•) binds quickly to CBS (k on ∼ 8 × 10(3) m(-1) s(-1))"
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Slow dissociation (koff approx. 0.003 s-1)
"dissociates slowly from the enzyme (k off ∼ 0.003 s(-1))"
Homocysteine contribution to DNA damage in cystathionine β-synthase-deficient patients.
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CBS-deficient patients have increased DNA damage
"We verified that DNA damage was significantly higher in the CBS-deficient patients under treatment"
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Homocysteine induces DNA damage in concentration-dependent manner
"the in vitro study showed a concentration-dependent effect of Hcy inducing DNA damage"
A proteome-scale map of the human interactome network.
A massively parallel pipeline to clone DNA variants and examine molecular phenotypes of human disease mutations.
An inter-species protein-protein interaction network across vast evolutionary distance.
Heme interaction of the intrinsically disordered N-terminal peptide segment of human cystathionine-β-synthase.
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N-terminal 40 residues are intrinsically disordered
"NMR spectroscopy revealed that the forty N-terminal residues constitute an intrinsically disordered region of the protein cystathionine-beta-synthase"
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Second heme-binding site via Cys15/His22 CP-motif
"the disordered N-terminal region of CBS contributes heme-binding capacities via a second binding site, the CP-based motif at cysteine-15"
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Heme binding increases enzyme activity by approx. 30%
"The functional assay reveals that this heme-binding site at cysteine-15 and histidine-22 as second axial heme ligand increases the efficacy of the enzyme by approx. 30%"
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
PXLP-CBS tetramers condenses HCYS and L-Ser to form L-Cystathionine
Deep research report on CBS