Biology subjects

Conter, C.

Publications and source records attributed to Conter, C..

2 recordsLinked to original sources

bioRxiv2024

Engineered Oxalate decarboxylase boosts activity and stability for biological applications

Oxalate decarboxylase (OxDC) from Bacillus subtilis is a Mn-dependent hexameric enzyme which converts oxalate to carbon dioxide and formate. Recently, OxDC has attracted the interest of the scientific community, due to its biotechnological and medical applications for the treatment of hyperoxalurias, a group of pathologic conditions associated with excessive oxalate urinary excretion due to either increased endogenous production or increased exogenous absorption. The fact that OxDC displays optimum pH in the acidic range, represents a big limitation for most biotechnological applications involving processes occurring at neutral pH, where the activity and stability of the enzyme are remarkably reduced. Here, through bioinformatics-guided protein engineering, followed by combinatorial mutagenesis and analyses of activity and thermodynamic stability, we identified a double mutant of OxDC endowed with enhanced catalytic efficiency and stability under physiological conditions. The obtained engineered form of OxDC offers a potential tool for improved intestinal oxalate degradation in hyperoxaluria patients.

biochemistry↗

bioRxiv2021

Structure of Cystathionine β-Synthase from Toxoplasma gondii, a key enzyme in its H2S production machinery.

Cystathionine {beta}-synthase (CBS), the pivotal enzyme of the reverse transsulfuration pathway, catalyzes the pyridoxal-5-phosphate-dependent condensation of serine with homocysteine to form cystathionine. Additionally, CBS performs alternative reactions that use homocysteine and cysteine as substrates leading to the endogenous biosynthesis of hydrogen sulfide (H2S), an important signal transducer in many physiological and pathological processes. Toxoplasma gondii, the causative agent of toxoplasmosis, encodes a functional CBS (TgCBS) that contrary to human CBS, is not allosterically regulated by S-adenosylmethionine and can use both, Ser and O-acetylserine (OAS) as substrates. TgCBS is also strongly implicated in the production of H2S, and thus involved in redox homeostasis of the parasite. Here, we report its crystal structure, the first CBS from a protozoan described so far. Our data reveals a basal-like fold that unexpectedly differs from the active conformations found in other organisms, but structurally similar to the pathogenic activated mutant D444N of the human enzyme.

biochemistry↗