HldE is a bifunctional enzyme in ADP-heptose precursor biosynthesis. Its N-terminal kinase phosphorylates D-glycero-D-manno-heptose 7-phosphate at C-1, and its C-terminal adenylyltransferase converts the resulting heptose 1-phosphate to ADP-D-glycero-beta-D-manno-heptose. Any subsequent C-6 epimerization to the L,D stereoisomer is performed by a separate HldD enzyme.
Definition: The chemical reactions and pathways resulting in the formation of ADP-D-glycero-beta-D-manno-heptose.
Justification: HldE forms the D,D-heptose nucleotide sugar directly, whereas the only specific GO process term names the downstream L,D stereoisomer. KT2440 lacks a resolved HldD ortholog, so the D,D endpoint must be representable without asserting terminal C-6 epimerization.
Parent term: nucleotide-sugar biosynthetic process
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: HldE is catalytic but has two much more informative assigned activities. Reason: GO:0033785 and GO:0033786 identify the kinase and adenylyltransferase reactions. |
| GO:0005524 ATP binding | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: Both HldE reactions use ATP. Reason: ATP binding is mechanistically compatible but less informative than either exact catalytic activity. |
| GO:0005829 cytosol | IEA GO_REF:0000118 | KEEP AS NON CORE | Summary: A soluble cytosolic location is compatible with ADP-heptose precursor synthesis. Reason: The TreeGrafter location is plausible but does not define HldE function. |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: HldE acts on phosphorylated heptose intermediates. Reason: This generic process does not distinguish ADP-heptose precursor biosynthesis. |
| GO:0016301 kinase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: The N-terminal HldE domain is a kinase. Reason: GO:0033785 captures the exact heptose 7-phosphate kinase activity. |
| GO:0016772 transferase activity, transferring phosphorus-containing groups | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Both HldE reactions transfer phosphorus-containing groups. Reason: The exact kinase and adenylyltransferase terms should carry the core assertions. |
| GO:0016773 phosphotransferase activity, alcohol group as acceptor | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: This broad phosphotransferase term describes the N-terminal reaction class. Reason: GO:0033785 specifies the heptose substrate and reaction position. |
| GO:0016779 nucleotidyltransferase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: The C-terminal domain transfers AMP to heptose 1-phosphate. Reason: GO:0033786 is the exact adenylyltransferase activity. |
| GO:0033785 heptose 7-phosphate kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: HldE phosphorylates D-glycero-D-manno-heptose 7-phosphate at C-1. Reason: The reviewed record, HAMAP rule, EC 2.7.1.167, Rhea 27473, UniRule, and PTN005327360 agree on this reaction. Supporting Evidence: file:PSEPK/hldE/hldE-uniprot.txt EC=2.7.1.167 |
| GO:0033786 heptose-1-phosphate adenylyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: HldE transfers ADP from ATP to D-glycero-beta-D-manno-heptose 1-phosphate. Reason: The reviewed record, HAMAP rule, EC 2.7.7.70, Rhea 27465, UniRule, and PTN005327360 agree on this reaction. Supporting Evidence: file:PSEPK/hldE/hldE-uniprot.txt EC=2.7.7.70 |
| GO:0097171 ADP-L-glycero-beta-D-manno-heptose biosynthetic process | IEA GO_REF:0000041 | UNDECIDED | Summary: HldE makes ADP-D-glycero-beta-D-manno-heptose, the immediate substrate for HldD in the canonical L,D-heptose route. Reason: The two HldE reactions are secure, but no HldD ortholog is resolved in KT2440. Until the inner-core heptose stereochemistry or a non-orthologous epimerase is established, the process term's L,D endpoint is uncertain for this strain. Supporting Evidence: file:projects/P_PUTIDA/deep-research/PSEPK__adp-heptose-biosynthesis__ppu00541-deep-research-openscientist.md The final step — the ADP-L-glycero-D-manno-heptose-6-epimerase HldD/GmhD |
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Download this section (compressed HTML)Q: Does KT2440 incorporate D,D-heptose directly into its LPS core, or is HldD chemistry supplied by a non-orthologous enzyme?
Experiment: Determine KT2440 LPS inner-core heptose stereochemistry and assay candidate NAD-dependent epimerases against ADP-D,D-heptose.
Type: structural glycomics and targeted enzyme screening
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