6W1H

Crystal structure of the hydroxyglutarate synthase in complex with 2-oxoadipate from Pseudomonas putida

Summary for 6W1H

• Entry DOI: 10.2210/pdb6w1h/pdb
• Descriptor: Hydroxyglutarate synthase, NICKEL (II) ION, 2-OXOADIPIC ACID, ... (4 entities in total)
• Functional Keywords: decarboxylase, lysine catabolism, lyase
• Biological source: Pseudomonas putida
• Total number of polymer chains: 1
• Total formula weight: 51646.62

Authors

Pereira, J.H.,Thompson, M.G.,Blake-Hedges, J.M.,Keasling, J.D.,Adams, P.D. (deposition date: 2020-03-04, release date: 2020-06-24, Last modification date: 2023-10-18)

Primary citation

Thompson, M.G.,Blake-Hedges, J.M.,Pereira, J.H.,Hangasky, J.A.,Belcher, M.S.,Moore, W.M.,Barajas, J.F.,Cruz-Morales, P.,Washington, L.J.,Haushalter, R.W.,Eiben, C.B.,Liu, Y.,Skyrud, W.,Benites, V.T.,Barnum, T.P.,Baidoo, E.E.K.,Scheller, H.V.,Marletta, M.A.,Shih, P.M.,Adams, P.D.,Keasling, J.D.
An iron (II) dependent oxygenase performs the last missing step of plant lysine catabolism.
Nat Commun, 11:2931-2931, 2020

PubMed Abstract: Despite intensive study, plant lysine catabolism beyond the 2-oxoadipate (2OA) intermediate remains unvalidated. Recently we described a missing step in the D-lysine catabolism of Pseudomonas putida in which 2OA is converted to D-2-hydroxyglutarate (2HG) via hydroxyglutarate synthase (HglS), a DUF1338 family protein. Here we solve the structure of HglS to 1.1 Å resolution in substrate-free form and in complex with 2OA. We propose a successive decarboxylation and intramolecular hydroxylation mechanism forming 2HG in a Fe(II)- and O-dependent manner. Specificity is mediated by a single arginine, highly conserved across most DUF1338 proteins. An Arabidopsis thaliana HglS homolog coexpresses with known lysine catabolism enzymes, and mutants show phenotypes consistent with disrupted lysine catabolism. Structural and biochemical analysis of Oryza sativa homolog FLO7 reveals identical activity to HglS despite low sequence identity. Our results suggest DUF1338-containing enzymes catalyze the same biochemical reaction, exerting the same physiological function across bacteria and eukaryotes.

PubMed: 32523014
DOI: 10.1038/s41467-020-16815-3

Experimental method

X-RAY DIFFRACTION (1.42 Å)