8BIZ

Cystathionine gamma-lyase from Toxoplasma gondii in complex with cysteine

8BIZ の概要

• エントリーDOI: 10.2210/pdb8biz/pdb
• 分子名称: Cystathionine beta-lyase, putative, PYRIDOXAL-5'-PHOSPHATE, CYSTEINE, ... (4 entities in total)
• 機能のキーワード: transsulfuration pathway, hydrogen sulfide, cysteine, toxoplasma, cytosolic protein
• 由来する生物種: Toxoplasma gondii
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 92645.59

構造登録者

Fernandez-Rodriguez, C.,Conter, C.,Oyenarte, I.,Favretto, F.,Quintana, I.,Martinez-Chantar, M.L.,Astegno, A.,Martinez-Cruz, L.A. (登録日: 2022-11-02, 公開日: 2023-04-12, 最終更新日: 2024-02-07)

主引用文献

Fernandez-Rodriguez, C.,Conter, C.,Oyenarte, I.,Favretto, F.,Quintana, I.,Martinez-Chantar, M.L.,Astegno, A.,Martinez-Cruz, L.A.
Structural basis of the inhibition of cystathionine gamma-lyase from Toxoplasma gondii by propargylglycine and cysteine.
Protein Sci., 32:e4619-e4619, 2023

PubMed Abstract: Cystathionine γ-lyase (CGL) is a PLP-dependent enzyme that catalyzes the last step of the reverse transsulfuration route for endogenous cysteine biosynthesis. The canonical CGL-catalyzed process consists of an α,γ-elimination reaction that breaks down cystathionine into cysteine, α-ketobutyrate, and ammonia. In some species, the enzyme can alternatively use cysteine as a substrate, resulting in the production of hydrogen sulfide (H S). Importantly, inhibition of the enzyme and consequently of its H S production activity, makes multiresistant bacteria considerably more susceptible to antibiotics. Other organisms, such as Toxoplasma gondii, the causative agent of toxoplasmosis, encode a CGL enzyme (TgCGL) that almost exclusively catalyzes the canonical process, with only minor reactivity to cysteine. Interestingly, the substitution of N360 by a serine (the equivalent amino acid residue in the human enzyme) at the active site changes the specificity of TgCGL for the catalysis of cystathionine, resulting in an enzyme that can cleave both the CγS and the CβS bond of cystathionine. Based on these findings and to deepen the molecular basis underlying the enzyme-substrate specificity, we have elucidated the crystal structures of native TgCGL and the variant TgCGL-N360S from crystals grown in the presence of cystathionine, cysteine, and the inhibitor d,l-propargylglycine (PPG). Our structures reveal the binding mode of each molecule within the catalytic cavity and help explain the inhibitory behavior of cysteine and PPG. A specific inhibitory mechanism of TgCGL by PPG is proposed.

PubMed: 36883335
DOI: 10.1002/pro.4619

実験手法

X-RAY DIFFRACTION (1.891 Å)