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

Nature Communications
Mitchell G ThompsonJay 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.

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Citations

May 17, 2021·Journal of Experimental Botany·Björn Heinemann, Tatjana M Hildebrandt
Nov 2, 2021·Journal of Experimental Botany·Qingqing YangQiaoquan Liu

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Datasets Mentioned

BETA
DUF1338

Methods Mentioned

BETA
enzyme
protein folding
PCR
genotyping

Software Mentioned

Vector Alignment Search Tool ( VAST )
Coot
j5
BlastP
VAST
Phenix
PyMOL
UCSF Chimera
ModelFinder
jalview

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