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.

中文翻译：

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刚地弓形虫胱硫醚β-合酶的结构，这是其硫化氢生产设备中的关键酶。

胱硫醚β合酶（CBS）是逆转硫磺途径的关键酶，催化丝氨酸与高半胱氨酸的5-磷酸吡ido醛依赖性缩合反应形成胱硫醚。此外，CBS还会执行其他反应，这些反应使用高半胱氨酸和半胱氨酸作为底物，导致内生生物合成硫化氢（H2S）的生物合成，硫化氢是许多生理和病理过程中的重要信号转导子。弓形虫病的病原体弓形虫编码的功能性CBS（TgCBS）与人的CBS相反，不受S-腺苷甲硫氨酸的变构调节，可以同时使用Ser和O-乙酰丝氨酸（OAS）作为底物。TgCBS也与H2S的产生密切相关，因此参与了该寄生虫的氧化还原稳态。在这里，我们报告其晶体结构，到目前为止，描述了原生动物的第一个CBS。我们的数据揭示了一个基底样的折叠，该折叠与其他生物体中发现的活性构象出乎意料的不同，但在结构上类似于人类酶的致病性活化突变体D444N。