9Y6T
Structure of Mycobacterium tuberculosis pyruvate dehydrogenase complex E2p core subunit DlaT in a hexamer state
This is a non-PDB format compatible entry.
Summary for 9Y6T
| Entry DOI | 10.2210/pdb9y6t/pdb |
| EMDB information | 72630 |
| Descriptor | Dihydrolipoyllysine-residue acetyltransferase component of pyruvate dehydrogenase complex (1 entity in total) |
| Functional Keywords | hexamer dihydrolipoamide acetyltransferase mycobacterium tuberculosis pyruvate dehydrogenase complex, transferase |
| Biological source | Mycobacterium tuberculosis |
| Total number of polymer chains | 6 |
| Total formula weight | 155708.47 |
| Authors | |
| Primary citation | Hsu, H.C.,Bonnet, I.,Bryk, R.,Li, H. Mycobacterium tuberculosis assembles a unique hexameric E2p core of the pyruvate dehydrogenase complex. J.Biol.Chem., :111284-111284, 2026 Cited by PubMed Abstract: The pyruvate dehydrogenase complex (PDHc) is a universally conserved multienzyme system that converts pyruvate into acetyl-CoA for entry into the TCA cycle and for NADH production. Its central scaffold, the dihydrolipoyl transacetylase (E2p), forms an oligomeric inner core that recruits pyruvate dehydrogenase (E1p) and dihydrolipoyl dehydrogenase (E3). All previously characterized PDHc assemblies adopt either an octahedral 24-mer or an icosahedral 60-mer E2p core, each constructed from trimeric building blocks. We recently showed that the Mycobacterium tuberculosis (Mtb) E2p protein DlaT also functions as the core of the pathogen's peroxynitrite reductase/peroxidase (PNR/P) complex. Here, using cryo-EM, we demonstrate that DlaT assembles into discrete hexamers and dodecamers at micromolar concentrations, which approximate intracellular DlaT concentrations in Mtb. Structure-guided mutagenesis combined with in vitro activity assays indicate that the hexamer represents the functional E2p core of the Mtb PDHc. This noncanonical architecture arises from unique interfaces between DlaT trimers that preclude formation of the classic spherical 24- or 60-mer structures. We propose that this specialized E2p organization enables Mtb to regulate metabolic activities and to remodel the E2p core for engagement in the PNR/P antioxidant pathway under stress. Our findings reveal an unexpected diversity in PDHc architecture and uncover a distinct organization principle for the core metabolic complex in mycobacteria. PubMed: 41690596DOI: 10.1016/j.jbc.2026.111284 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.65 Å) |
Structure validation
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