PDBsum entry 6w1h

Lyase

PDB id: 6w1h

Contents

Protein chain

450 a.a.

Ligands

OOG

Metals

_NI

Waters ×664

PDB id:

6w1h

Name:

Lyase

Title:

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

Structure:

Hydroxyglutarate synthase. Chain: a. Engineered: yes

Source:

Pseudomonas putida. Organism_taxid: 303. Gene: ydcj, pp_5260. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.42Å R-factor: 0.159 R-free: 0.194

Authors:

J.H.Pereira,M.G.Thompson,J.M.Blake-Hedges,J.D.Keasling,P.D.Adams

Key ref:

M.G.Thompson et al. (2020). An iron (II) dependent oxygenase performs the last missing step of plant lysine catabolism. Nat Commun, 11, 2931. PubMed id: 32523014 DOI: 10.1038/s41467-020-16815-3

Date:

04-Mar-20 Release date: 24-Jun-20

Protein chain

Q88CC1  (Q88CC1_PSEPK) -  2-oxoadipate dioxygenase/decarboxylase from Pseudomonas putida (strain ATCC 47054 / DSM 6125 / CFBP 8728 / NCIMB 11950 / KT2440)

Seq: 464 a.a.

Struc: 450 a.a.

Enzyme reactions

• Enzyme class: E.C.1.13.11.93 - 2-oxoadipate dioxygenase/decarboxylase.
• Reaction: 2-oxoadipate + O2 = (R)-2-hydroxyglutarate + CO2

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1038/s41467-020-16815-3

Nat Commun 11:2931 (2020)

PubMed id: 32523014

An iron (II) dependent oxygenase performs the last missing step of plant lysine catabolism.

M.G.Thompson, J.M.Blake-Hedges, J.H.Pereira, J.A.Hangasky, M.S.Belcher, W.M.Moore, J.F.Barajas, P.Cruz-Morales, L.J.Washington, R.W.Haushalter, C.B.Eiben, Y.Liu, W.Skyrud, V.T.Benites, T.P.Barnum, E.E.K.Baidoo, H.V.Scheller, M.A.Marletta, P.M.Shih, P.D.Adams, J.D.Keasling.

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 O₂-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.