Cystathionine β-lyase

Cystathionine β-lyase is an enzyme that breaks down cystathionase. There are two kinds of β-cystathionase and γ-cystathionase. Both types use pyridoxal phosphate as a coenzyme. β-cystathionase decomposes cystic sulfuric acid into homocysteine, ammonia and pyruvate, which are found in bacteria and bread mold. The decomposition products produced by γ-cystathionine catalysis are cysteine, ammonia and α-ketobutyric acid, which are present in the liver and bread mold.

Introductions

Cystathionine β-lyase was found in plants and microbes is a pyridoxal-5′-phosphate (PLP)-dependent homotetrameric enzyme of approximately 35–40 kDa and catalyses the penultimate step of methionine biosynthesis, that is, α, β-elimination reaction, where cystathionine is hydrolysed into pyruvate, ammonia, and homocysteine. Subsequently, homocysteine gets methylated to methionine. The overexpression of CBL encoding metC gene in D-alanine gene knockout models of several bacteria was found to be significant for their sustenance in host cell environment. In addition, CBL also dictated the virulence of Salmonella enterica thus playing a decisive role in its pathogenicity.

Structure

Cystathionine β-synthase (CBS) is a homotetramer in the cytoplasm, composed of 63 KD subunits, and is a pyridoxal phosphate (PLP) dependent enzyme. Cystathionine β-lyase is constructed as a dimer of dimers, each associated with a PLP molecule bound to the catalytic site via a lysine residue. Dimers are formed from two monomers that are associated through several electrostatic, hydrogen bonding, and hydrophobic interactions, while tetramers are stabilized by the interaction between the N-terminal domain and the key alpha helix. Under the catalysis of vitamin B6, CBS can make serine and homocysteine (homocysteine, Hcy) to synthesize cystathionine. As a key enzyme that affects the level of Hcy, CBS plays a pivotal role in the path of sulfuric acid conversion from Hcy to cystathionine. This enzyme is used for the detection of homocysteine in the blood in enzyme cycling methodology.

Figure 1. Structure of Cystathionine β-synthase (CBS).

Functions

The catabolism of sulfur-containing amino acids plays an important role in the development of cheese flavor. It is believed that during maturation, cystathionine β-lyase (CBL) contributes to the formation of volatile sulfur compounds (VSC) such as methyl mercaptan and dimethyl disulfide. However, the role of CBL in the production of VSC in the catabolism of specific sulfur-containing amino acids is unclear. Cystathionine β-lyase (CBL) is a pyridoxal 5'-phosphate (PLP) dependent enzyme, purified and cloned from Lactococcus lactis. CBL is involved in the alpha, beta-elimination of cystathionine, forming homocysteine, pyruvate, and ammonia. CBL from Lactococcus lactis can also catalyze the conversion of methionine to methyl mercaptan. Compared with wild strains, the CBL overexpression variants of Lactococcus lactis have been shown to produce more VSC with methionine as a substrate, suggesting a possible mechanism for increasing the production of VSC in cheese. However, this method may be more valuable in the application of lactobacillus strains with metabolic activity during cheese fermentation. The role of CBL and catabolic pathways responsible for the formation of VSC from sulfur amino acids/derivatives has not been well characterized in Lactobacillus.

Side effects

Cystathionase is associated with the onset of cerebral infarction. Cystathionine β-synthase is a key enzyme for homocysteine metabolism, and its genetic mutation is not a potential genetic candidate for cerebral infarction. The relationship between cystathionine-β synthase (CBS) gene polymorphism and type 2 diabetes is one of the key enzymes of cystathionase metabolism.

Significances

Cystathionine β-lyase catalyzes the production of homocysteine, which is the direct precursor of methionine. Methionine is an essential amino acid for bacteria and is required for protein synthesis and S-adenosylmethionine synthesis; therefore, amino acids are directly related to DNA replication. Due to its necessity in DNA replication, inhibition of cystathionine β-lyase is an attractive antibiotic target. In addition, this enzyme does not exist in the human body, thereby reducing the possibility of harmful and harmful side effects. Studies have linked the antifungal activity of several antifungal agents to the inhibition of cystathionine β-lyase. However, other studies have not observed the inhibitory effect of these enzymes on the enzyme. To further study the inhibitory effect of cysteine on β-lyase has a comprehensive significance for the growth of microorganisms and fungi.

Reference

1. Ejim LJ, et al. Inhibitors of bacterial cystathionine beta-lyase: leads for new antimicrobial agents and probes of enzyme structure and function. Journal of Medicinal Chemistry. 2007,50 (4): 755-64.