6XWL

Cystathionine beta-synthase from Toxoplasma gondii

Summary for 6XWL

• Entry DOI: 10.2210/pdb6xwl/pdb
• Related: 1JBQ 4L0D
• Descriptor: Cystathionine beta-synthase, PYRIDOXAL-5'-PHOSPHATE (2 entities in total)
• Functional Keywords: transulfuration, hydrogen sulfide, homocysteine, cbs, cytosolic protein
• Biological source: Toxoplasma gondii ME49
• Total number of polymer chains: 6
• Total formula weight: 337232.49

Authors

Fernandez-Rodriguez, C.,Oyenarte, I.,Conter, C.,Gonzalez-Recio, I.,Quintana, I.,Martinez-Chantar, M.,Astegno, A.,Martinez-Cruz, L.A. (deposition date: 2020-01-23, release date: 2021-02-03, Last modification date: 2024-01-24)

Primary citation

Fernandez-Rodriguez, C.,Oyenarte, I.,Conter, C.,Gonzalez-Recio, I.,Nunez-Franco, R.,Gil-Pitarch, C.,Quintana, I.,Jimenez-Oses, G.,Dominici, P.,Martinez-Chantar, M.L.,Astegno, A.,Martinez-Cruz, L.A.
Structural insight into the unique conformation of cystathionine beta-synthase from Toxoplasma gondii .
Comput Struct Biotechnol J, 19:3542-3555, 2021

PubMed Abstract: Cysteine plays a major role in the redox homeostasis and antioxidative defense mechanisms of many parasites of the phylum Apicomplexa. Of relevance to human health is , the causative agent of toxoplasmosis. A major route of cysteine biosynthesis in this parasite is the reverse transsulfuration pathway involving two key enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL). CBS from (CBS) catalyzes the pyridoxal-5́-phosphate-dependent condensation of homocysteine with either serine or -acetylserine to produce cystathionine. The enzyme can perform alternative reactions that use homocysteine and cysteine as substrates leading to the endogenous biosynthesis of hydrogen sulfide, another key element in maintaining the intracellular redox equilibrium. In contrast with human CBS, CBS lacks the N-terminal heme binding domain and is not responsive to S-adenosylmethionine. Herein, we describe the structure of a CBS construct that lacks amino acid residues 466-491 and shows the same activity of the native protein. CBS Δ466-491 was determined alone and in complex with reaction intermediates. A complementary molecular dynamics analysis revealed a unique domain organization, similar to the pathogenic mutant D444N of human CBS. Our data provides one missing piece in the structural diversity of CBSs by revealing the so far unknown three-dimensional arrangement of the CBS-type of Apicomplexa. This domain distribution is also detected in yeast and bacteria like . These results pave the way for understanding the mechanisms by which CBS regulates the intracellular redox of the parasite, and have far-reaching consequences for the functional understanding of CBSs with similar domain distribution.

PubMed: 34194677
DOI: 10.1016/j.csbj.2021.05.052

Experimental method

X-RAY DIFFRACTION (3.201 Å)