10gw | pdb_000010gw
Crystal structure of tetrameric 6-phosphogluconate dehydrogenase from Gluconobacter oxydans in complex with 6-phosphogluconate
Structural highlights
Function6PGDH_GLUOX Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NAD to NADH.[1] Publication Abstract from PubMed6-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 2.0â¯A 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. Structural, dynamic, and evolutionary determinants of substrate binding in the tetrameric 6-phosphogluconate dehydrogenase from Gluconobacter oxydans.,Maturana P, Villalobos P, Roversi P, Cabrera R Arch Biochem Biophys. 2026 May;779:110779. doi: 10.1016/j.abb.2026.110779. Epub , 2026 Feb 28. PMID:41765070[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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