HglS is a 2-oxoadipate dioxygenase/decarboxylase that catalyzes the final step in D-lysine catabolism by converting 2-oxoadipate to D-2-hydroxyglutarate through an Fe(II)- and O2-dependent mechanism involving successive decarboxylation and intramolecular hydroxylation. The enzyme shows high specificity for 2-oxoadipate (KM ~0.01-0.06 mM) and is essential for growth on both L-lysine and D-lysine. HglS belongs to the DUF1338 family and represents the last missing enzymatic step in plant lysine catabolism that was identified through high-resolution crystal structures (PDB: 6W1G, 6W1H) which revealed the molecular basis for substrate specificity mediated by a conserved arginine residue (Arg74).
Definition: Catalysis of the oxidative decarboxylation of 2-oxoadipate to form D-2-hydroxyglutarate using Fe(II) and O2 as cofactors
Justification: HglS represents a specific type of dioxygenase activity with unique substrate specificity. A more specific term would better capture this distinct enzymatic function than the general dioxygenase activity term.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016491 oxidoreductase activity | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Accurate but general - HglS is specifically a dioxygenase/decarboxylase Reason: While correct, this term is too general. The more specific dioxygenase activity term better captures HglS function. |
| GO:0051213 dioxygenase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Correct and specific - HglS performs dioxygenase activity on 2-oxoadipate Reason: Accurately describes the core molecular function. HglS is a Fe(II)-dependent dioxygenase that incorporates O2 during the oxidative decarboxylation of 2-oxoadipate. |
| GO:0019477 L-lysine catabolic process | IMP PMID:31064836 Massively parallel fitness profiling reveals multiple novel ... | NEW | Summary: Core biological process - HglS is essential for lysine catabolism. Term updated from obsolete GO:0006554 to GO:0019477. Reason: HglS catalyzes a key step in lysine breakdown and deletion mutants cannot grow on lysine. Original term GO:0006554 was obsoleted in favor of more specific terms. Supporting Evidence: PMID:31064836 Massively Parallel Fitness Profiling Reveals Multiple Novel Enzymes in Pseudomonas putida Lysine Metabolism. |
| GO:0042180 ketone metabolic process | IDA PMID:31064836 Massively parallel fitness profiling reveals multiple novel ... | NEW | Summary: Specific metabolic process - HglS processes 2-oxoadipate (a ketone derivative) Reason: The substrate 2-oxoadipate is a ketone derivative and the reaction involves ketone metabolism. Supporting Evidence: PMID:31064836 Massively Parallel Fitness Profiling Reveals Multiple Novel Enzymes in Pseudomonas putida Lysine Metabolism. |
| GO:0006520 amino acid metabolic process | IMP PMID:31064836 Massively parallel fitness profiling reveals multiple novel ... | NEW | Summary: Broad metabolic process - HglS functions in amino acid catabolism Reason: As part of lysine catabolism, HglS participates in amino acid metabolic processes. Supporting Evidence: PMID:31064836 Massively Parallel Fitness Profiling Reveals Multiple Novel Enzymes in Pseudomonas putida Lysine Metabolism. |
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Download this section (compressed HTML)Q: How does HglS coordinate with other enzymes in the lysine catabolic pathway?
Suggested experts: Bacterial metabolism specialists, Enzyme biochemists, Systems biologists
Q: What is the evolutionary origin of the DUF1338 family and how did substrate specificity evolve?
Suggested experts: Evolutionary biochemists, Comparative genomics researchers, Structural biologists
Q: Can HglS be engineered for biotechnological production of D-2-hydroxyglutarate or related compounds?
Suggested experts: Enzyme engineers, Synthetic biologists, Metabolic engineers
Experiment: Systematic comparison of HglS substrate specificity across different 2-oxo acids to fully define the substrate scope and identify any secondary activities.
Type: Comparative enzymatic analysis
Experiment: Site-directed mutagenesis of residues beyond Arg74 to understand the complete molecular basis for substrate specificity and catalytic mechanism.
Type: Structural-functional analysis
Experiment: Comprehensive analysis of DUF1338 family members across bacteria and eukaryotes to understand evolutionary conservation and functional divergence.
Type: Phylogenetic analysis
Experiment: Complete mapping of lysine catabolism pathway in P. putida to understand HglS integration with upstream and downstream enzymes.
Type: Metabolic pathway analysis
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