9SML
Structure of trans-basal conformer of human CBS trapped in PLP-serine external aldemine intermediate (CBS-PLP-Ser)- by Helical approach
Summary for 9SML
| Entry DOI | 10.2210/pdb9sml/pdb |
| EMDB information | 55037 |
| Descriptor | Cystathionine beta-synthase, PROTOPORPHYRIN IX CONTAINING FE, (E)-N-({3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]pyridin-4-yl}methylidene)-L-serine (3 entities in total) |
| Functional Keywords | transsulfuration pathway, l-serine hydro-lyase, heme-binding protein, cbs domain, lyase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 6 |
| Total formula weight | 344120.34 |
| Authors | Inayathulla, M.,Tomas, M. (deposition date: 2025-09-08, release date: 2026-07-29, Last modification date: 2026-08-05) |
| Primary citation | 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 Cited by 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: 42248820DOI: 10.1038/s41467-026-73198-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.78 Å) |
Structure validation
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