9SI8

Structure of trans-basal conformer of human CBS trapped in PLP-aminoacrylate intermediate state (CBS PLP-AA)- by Helical processing.

9SI8 の概要

• エントリーDOI: 10.2210/pdb9si8/pdb
• EMDBエントリー: 54925
• 分子名称: Cystathionine beta-synthase, PROTOPORPHYRIN IX CONTAINING FE, 2-[({3-HYDROXY-2-METHYL-5-[(PHOSPHONOOXY)METHYL]PYRIDIN-4-YL}METHYL)AMINO]ACRYLIC ACID (3 entities in total)
• 機能のキーワード: transsulfuration pathway, l-serine hydro-lyase, heme-binding protein, cbs domain, lyase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 344024.35

構造登録者

Inayathulla, M.,Tomas, M. (登録日: 2025-08-28, 公開日: 2026-07-29, 最終更新日: 2026-08-05)

主引用文献

Mohammed, I.,Mijatovic, E.,Philipp, T.M.,Janickova, L.,Ascencao, K.,Asturias, F.J.,Martinez-Cruz, L.A.,Szabo, C.,Stahlberg, H.,Majtan, T.
Structural basis for a filamentous morpheein model of human cystathionine beta-synthase.
Nat Commun, 17:-, 2026

PubMed Abstract: Human cystathionine beta-synthase (CBS) is a vital enzyme that regulates sulfur amino acid metabolism, hydrogen sulfide production, and cellular redox balance. Using a multidisciplinary approach, we demonstrate that CBS functions as a filamentous morpheein, with its stability, turnover, and activity governed by dynamic quaternary structural transitions. Three distinct filamentous assemblies were resolved by cryo-EM and are mediated by the oligomerization loop (residues 516-525): (i) ligand-free trans-dimers that form trans-basal filaments with basal stability and activity, (ii) adenosylornithine-bound cis-dimers that assemble into stabilized cis-basal filaments and (iii) S-adenosylmethionine-bound allo-dimers, which, together with cis-dimers, form highly stable, allo-activated stacked filaments. These reversible filamentous assemblies redefine CBS biology by integrating oligomerization and allosteric regulation within a morpheein framework. These findings provide a transformative perspective on CBS function and open avenues for pharmacological targeting of dysregulated CBS in various diseases including homocystinuria, cancer, and Down syndrome.

PubMed: 42248820
DOI: 10.1038/s41467-026-73198-7

実験手法

ELECTRON MICROSCOPY (2.47 Å)