Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.2.1.22 (cystathionine beta-synthase)
 965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CBS (cystathionine beta-synthase) domains are found in proteins from all kingdoms of life, and point mutations in these domains are responsible for a variety of hereditary diseases in humans; however, the functions of CBS domains are not well understood. In the present study, we cloned, expressed in Escherichia coli, and characterized a family II PPase (inorganic pyrophosphatase) from Moorella thermoacetica (mtCBS-PPase) that has a pair of tandem 60-amino-acid CBS domains within its N-terminal domain. Because mtCBS-PPase is a dimer and requires transition metal ions (Co2+ or Mn2+) for activity, it resembles common family II PPases, which lack CBS domains. The mtCBS-PPase, however, has lower activity than common family II PPases, is potently inhibited by ADP and AMP, and is activated up to 1.6-fold by ATP. Inhibition by AMP is competitive, whereas inhibition by ADP and activation by ATP are both of mixed types. The nucleotides are effective at nanomolar (ADP) or micromolar concentrations (AMP and ATP) and appear to compete for the same site on the enzyme. The nucleotide-binding affinities are thus 100-10000-fold higher than for other CBS-domain-containing proteins. Interestingly, genes encoding CBS-PPase occur most frequently in bacteria that have a membrane-bound H+-translocating PPase with a comparable PP(i)-hydrolysing activity. Our results suggest that soluble nucleotide-regulated PPases act as amplifiers of metabolism in bacteria by enhancing or suppressing ATP production and biosynthetic reactions at high and low [ATP]/([AMP]+[ADP]) ratios respectively.
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PMID:A CBS domain-containing pyrophosphatase of Moorella thermoacetica is regulated by adenine nucleotides. 1771 78

Cystathionine beta-synthase (CBS), a key enzyme in the metabolism of homocysteine, has previously been shown to require a heme co-factor for maximal activity. However, the biochemical function of the CBS heme is not well defined. Here, we show that expression of human CBS in heme-deficient strains of Saccharomyces cerevisiae and Escherichia coli results in production of an enzyme that is misfolded and degraded. Addition of exogenous heme, porphyrins with non-iron metal, or porphyrin lacking metal entirely produced stable and active CBS enzyme. Purification of recombinant CBS enzyme expressed in the presence of various metalloporphyrins confirmed that Mn(III) and Co(III) had 30-60% of the specific activity of Fe(III)-CBS, and still responded to allosteric activation by S-adenosyl-L-methionine. Treatment of S. cerevisiae with the chemical chaperone trimethylamine-N-oxide resulted in near complete restoration of function to human CBS produced in a heme-deficient strain. Taken together, these results suggest that porphyrin moiety of the heme plays a critical role in proper CBS folding and assembly, but that the metal ion is not essential for this function or for allosteric regulation by S-adenosyl-L-methionine.
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PMID:Active cystathionine beta-synthase can be expressed in heme-free systems in the presence of metal-substituted porphyrins or a chemical chaperone. 1884 66

Phragmites australis, which is widely distributed throughout the world, is often used in the phytoremediation of acid mine drainage (AMD) due to its various mechanisms for survival under extremely harsh conditions. To explore the different responses of different aerial organs of P. australis to stress, soil and plant samples were collected from the AMD-polluted area of the Tongling mining area. The contents of manganese (Mn), iron (Fe), copper (Cu), zinc (Zn), arsenic (As), cadmium (Cd), and lead (Pb) in the soil and the leaf blades, leaf sheaths, and stems of P. australis as well as the contents/activities of cysteine synthase (CSase), superoxide dismutase (SOD), peroxidase (POD), glutathione (GSH), malondialdehyde (MDA), and proline (Pro) in the organs were determined. Our results revealed that the leaf sheath had the highest potential to store metals of all the organs. The highest translocation factor (TF) for Fe was observed from the stems to the leaf sheaths. A higher bioconcentration factor (BCF) for Mn was found in the leaf blades and leaf sheaths, while higher BCFs for Cd and Zn were observed in the stems. The content/activity of enzymatic and non-enzymatic stress-resistance substances varied from organ to organ. In general, the leaf sheaths remained almost as or slightly less stress-resistant than the leaf blades. It can be concluded that different plant organs play different roles in stress resistance, and understanding the tolerance mechanism of leaf sheaths to metals is essential for the application of phytoremediation procedures.
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PMID:Physiological responses and metal distributions of different organs of Phragmites australis shoots under acid mine drainage stress. 3291 62