10GW

Crystal structure of tetrameric 6-phosphogluconate dehydrogenase from Gluconobacter oxydans in complex with 6-phosphogluconate

Summary for 10GW

• Entry DOI: 10.2210/pdb10gw/pdb
• Descriptor: 6-phosphogluconate dehydrogenase, 6-PHOSPHOGLUCONIC ACID (3 entities in total)
• Functional Keywords: oxidative pentose phosphate pathway, 6-phosphogluconate dehydrogenase, dehydrogenase, oxidoreductase
• Biological source: Gluconobacter oxydans
• Total number of polymer chains: 4
• Total formula weight: 154432.70

Authors

Maturana, P.,Roversi, P.,Villalobos, P.,Gonzalez-Ordenes, F.,Castro-Fernandez, V.,Cabrera, R. (deposition date: 2026-01-19, release date: 2026-03-18)

Primary citation

Maturana, P.,Villalobos, P.,Roversi, P.,Cabrera, R.
Structural, dynamic, and evolutionary determinants of substrate binding in the tetrameric 6-phosphogluconate dehydrogenase from Gluconobacter oxydans.
Arch.Biochem.Biophys., 779:110779-110779, 2026

PubMed Abstract: 6-Phosphogluconate dehydrogenases (6PGDHs) catalyze a key oxidative step in the oxidative pentose phosphate pathway (oxPPP), a route essential for NAD(P)H generation and carbon metabolism in bacteria and eukaryotes. While the structural basis of substrate recognition is well established for long-chain dimeric 6PGDHs, the mechanisms used by short-chain tetrameric enzymes remain poorly defined. Here, we present a 2.0 Å crystal structure of tetrameric 6PGDH from Gluconobacter oxydans (Go6PGDH) in complex with 6-phosphogluconate (6PG) and integrate it with evolutionary, computational, and functional analyses. The structure shows that, unlike dimeric homologs, tetrameric Go6PGDH does not undergo a domain-closure transition upon ligand binding. Instead, 6PG induces a compaction of the tetramer mediated by two conserved C-terminal elements: an inter-protomer ionic "lock" and an intra-subunit C-terminal "latch" that together stabilize a closed catalytic pocket. Molecular-dynamics simulations identify His328 as a central residue that couples C-terminal tail closure to direct ligand coordination, and mutagenesis analysis confirms its essential role in catalytic efficiency. Thermodynamic measurements reveal that 6PG binding is strongly enthalpy-driven, consistent with the formation of an ordered hydrogen-bonding and electrostatic network in the closed conformation. These findings define a substrate-induced quaternary-tightening mechanism unique to tetrameric 6PGDHs and illustrate how a conserved C-terminal module has been adapted across the family to regulate substrate binding and catalysis.

PubMed: 41765070
DOI: 10.1016/j.abb.2026.110779

Experimental method

X-RAY DIFFRACTION (2 Å)