ADP-L-glycero-beta-D-manno-heptose biosynthesis
MetaCyc:PWY0-1241
The complete five-reaction MetaCyc route converts sedoheptulose 7-phosphate to ADP-L-glycero-beta-D-manno-heptose using GmhA, the two activities of HldE, GmhB and HldD. The selected proteins are E. coli K-12; native complexes are MG1655 assignments. The 2002 HldE/GmhB experiments used K-12 gene products with an Aneurinibacillus GmhA reagent, whereas later GmhA work directly examines E. coli. Current Rhea represents GmhA as two substrate molecules giving one alpha and one beta heptose 7-phosphate; both products and the coefficient are retained, without asserting an experimentally fixed 1:1 physiological product ratio. Only the beta branch continues to ADP-heptose. GmhA, HldE and HldD are represented by source-defined tetramer, dimer and pentamer assemblies; GmhB is monomeric. GmhA zinc is a similarity-based annotation. GmhB catalytic magnesium and manganese/cobalt alternatives are distinguished from its bound zinc loop site, whose physiological role remains unresolved. HldD recycles bound NADP during epimerization; NAD is a lower-activity substitute, not an additional required cofactor. Sedoheptulose generation, alpha-GDP-heptose synthesis, LPS incorporation and host sensing are outside this native boundary. No obligatory growth phenotype, universal strain activity or compensating GmhB phosphatase is inferred.
- Pathway type
- adp l glycero beta d manno heptose biosynthesis
- Organism scope
Pathway network
32 nodes · 43 asserted directed edges
Arrows show recorded subject → object relationships, not necessarily metabolic flow. Select a node for details or an arrow for evidence. Scroll, zoom or find a node to explore.
- Reaction / activity
- Chemical / cofactor
- Protein / complex
- Pathway
- Solid arrow: mechanistic relation
- Dashed arrow: membership, location or cofactor relation
Components and activities
| Node | Kind or role | Source direction |
|---|---|---|
Escherichia coli K-12NCBITaxon:83333 | taxon | |
waterCHEBI:15377 | small molecule | |
hydronCHEBI:15378 | small molecule | |
magnesium(2+)CHEBI:18420 | cofactor | |
manganese(2+)CHEBI:29035 | cofactor | |
zinc(2+)CHEBI:29105 | cofactor | |
ATP(4-)CHEBI:30616 | small molecule | |
diphosphate(3-)CHEBI:33019 | small molecule | |
hydrogenphosphateCHEBI:43474 | small molecule | |
ADP(3-)CHEBI:456216 | small molecule | |
cobalt(2+)CHEBI:48828 | cofactor | |
sedoheptulose 7-phosphate(2-)CHEBI:57483 | small molecule | |
NAD(1-)CHEBI:57540 | cofactor | |
NADP(3-)CHEBI:58349 | cofactor | |
ADP-D-glycero-beta-D-manno-heptose(2-)CHEBI:59967 | small molecule | |
D-glycero-alpha-D-manno-heptose 7-phosphate(2-)CHEBI:60203 | small molecule | |
D-glycero-beta-D-manno-heptose 7-phosphate(2-)CHEBI:60204 | small molecule | |
D-glycero-beta-D-manno-heptose 1,7-bisphosphate(4-)CHEBI:60208 | small molecule | |
ADP-L-glycero-beta-D-manno-heptose(2-)CHEBI:61506 | small molecule | |
D-glycero-beta-D-manno-heptose 1-phosphate(2-)CHEBI:61593 | small molecule | |
Phosphoheptose isomeraseUniProtKB:P63224 | protein | |
Bifunctional protein HldEUniProtKB:P76658 | protein | |
D-glycero-beta-D-manno-heptose-1,7-bisphosphate 7-phosphataseUniProtKB:P63228 | protein | |
ADP-L-glycero-D-manno-heptose-6-epimeraseUniProtKB:P67910 | protein | |
D-sedoheptulose 7-phosphate isomeraseMetaCyc:CPLX0-7660 | complex | |
fused heptose 7-phosphate kinase/heptose 1-phosphate adenyltransferaseMetaCyc:CPLX0-3661 | complex | |
ADP-L-glycero-D-mannoheptose 6-epimeraseMetaCyc:CPLX0-3681 | complex | |
2 D-sedoheptulose 7-phosphate => D-glycero-alpha-D-manno-heptose 7-phosphate + D-glycero-beta-D-manno-heptose 7-phosphateRHEA:27490 | molecular activity | left to right |
D-glycero-beta-D-manno-heptose 7-phosphate + ATP => D-glycero-beta-D-manno-heptose 1,7-bisphosphate + ADP + H(+)RHEA:27474 | molecular activity | left to right |
D-glycero-beta-D-manno-heptose 1,7-bisphosphate + H2O => D-glycero-beta-D-manno-heptose 1-phosphate + phosphateRHEA:28519 | molecular activity | left to right |
D-glycero-beta-D-manno-heptose 1-phosphate + ATP + H(+) => ADP-D-glycero-beta-D-manno-heptose + diphosphateRHEA:27466 | molecular activity | left to right |
ADP-D-glycero-beta-D-manno-heptose => ADP-L-glycero-beta-D-manno-heptoseRHEA:17578 | molecular activity | left to right |
Mechanistic edges
| Subject | Predicate and description | Object | Evidence |
|---|---|---|---|
sedoheptulose 7-phosphate(2-)CHEBI:57483 | consumes This is the formal Rhea two-anomer equation, not a measured fixed in vivo product ratio. | 2 D-sedoheptulose 7-phosphate => D-glycero-alpha-D-manno-heptose 7-phosphate + D-glycero-beta-D-manno-heptose 7-phosphateRHEA:27490 |
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2 D-sedoheptulose 7-phosphate => D-glycero-alpha-D-manno-heptose 7-phosphate + D-glycero-beta-D-manno-heptose 7-phosphateRHEA:27490 | produces This is the formal Rhea two-anomer equation, not a measured fixed in vivo product ratio. | D-glycero-alpha-D-manno-heptose 7-phosphate(2-)CHEBI:60203 |
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2 D-sedoheptulose 7-phosphate => D-glycero-alpha-D-manno-heptose 7-phosphate + D-glycero-beta-D-manno-heptose 7-phosphateRHEA:27490 | produces This is the formal Rhea two-anomer equation, not a measured fixed in vivo product ratio. | D-glycero-beta-D-manno-heptose 7-phosphate(2-)CHEBI:60204 |
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D-glycero-beta-D-manno-heptose 7-phosphate(2-)CHEBI:60204 | consumes | D-glycero-beta-D-manno-heptose 7-phosphate + ATP => D-glycero-beta-D-manno-heptose 1,7-bisphosphate + ADP + H(+)RHEA:27474 |
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ATP(4-)CHEBI:30616 | consumes | D-glycero-beta-D-manno-heptose 7-phosphate + ATP => D-glycero-beta-D-manno-heptose 1,7-bisphosphate + ADP + H(+)RHEA:27474 |
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D-glycero-beta-D-manno-heptose 7-phosphate + ATP => D-glycero-beta-D-manno-heptose 1,7-bisphosphate + ADP + H(+)RHEA:27474 | produces | D-glycero-beta-D-manno-heptose 1,7-bisphosphate(4-)CHEBI:60208 |
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D-glycero-beta-D-manno-heptose 7-phosphate + ATP => D-glycero-beta-D-manno-heptose 1,7-bisphosphate + ADP + H(+)RHEA:27474 | produces | ADP(3-)CHEBI:456216 |
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D-glycero-beta-D-manno-heptose 7-phosphate + ATP => D-glycero-beta-D-manno-heptose 1,7-bisphosphate + ADP + H(+)RHEA:27474 | produces | hydronCHEBI:15378 |
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D-glycero-beta-D-manno-heptose 1,7-bisphosphate(4-)CHEBI:60208 | consumes | D-glycero-beta-D-manno-heptose 1,7-bisphosphate + H2O => D-glycero-beta-D-manno-heptose 1-phosphate + phosphateRHEA:28519 |
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waterCHEBI:15377 | consumes | D-glycero-beta-D-manno-heptose 1,7-bisphosphate + H2O => D-glycero-beta-D-manno-heptose 1-phosphate + phosphateRHEA:28519 |
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D-glycero-beta-D-manno-heptose 1,7-bisphosphate + H2O => D-glycero-beta-D-manno-heptose 1-phosphate + phosphateRHEA:28519 | produces | D-glycero-beta-D-manno-heptose 1-phosphate(2-)CHEBI:61593 |
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D-glycero-beta-D-manno-heptose 1,7-bisphosphate + H2O => D-glycero-beta-D-manno-heptose 1-phosphate + phosphateRHEA:28519 | produces | hydrogenphosphateCHEBI:43474 |
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D-glycero-beta-D-manno-heptose 1-phosphate(2-)CHEBI:61593 | consumes | D-glycero-beta-D-manno-heptose 1-phosphate + ATP + H(+) => ADP-D-glycero-beta-D-manno-heptose + diphosphateRHEA:27466 |
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ATP(4-)CHEBI:30616 | consumes | D-glycero-beta-D-manno-heptose 1-phosphate + ATP + H(+) => ADP-D-glycero-beta-D-manno-heptose + diphosphateRHEA:27466 |
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hydronCHEBI:15378 | consumes | D-glycero-beta-D-manno-heptose 1-phosphate + ATP + H(+) => ADP-D-glycero-beta-D-manno-heptose + diphosphateRHEA:27466 |
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D-glycero-beta-D-manno-heptose 1-phosphate + ATP + H(+) => ADP-D-glycero-beta-D-manno-heptose + diphosphateRHEA:27466 | produces | ADP-D-glycero-beta-D-manno-heptose(2-)CHEBI:59967 |
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D-glycero-beta-D-manno-heptose 1-phosphate + ATP + H(+) => ADP-D-glycero-beta-D-manno-heptose + diphosphateRHEA:27466 | produces | diphosphate(3-)CHEBI:33019 |
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ADP-D-glycero-beta-D-manno-heptose(2-)CHEBI:59967 | consumes | ADP-D-glycero-beta-D-manno-heptose => ADP-L-glycero-beta-D-manno-heptoseRHEA:17578 |
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ADP-D-glycero-beta-D-manno-heptose => ADP-L-glycero-beta-D-manno-heptoseRHEA:17578 | produces | ADP-L-glycero-beta-D-manno-heptose(2-)CHEBI:61506 |
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D-sedoheptulose 7-phosphate isomeraseMetaCyc:CPLX0-7660 | catalyzes The selected biosynthetic direction does not assert irreversible chemistry. | 2 D-sedoheptulose 7-phosphate => D-glycero-alpha-D-manno-heptose 7-phosphate + D-glycero-beta-D-manno-heptose 7-phosphateRHEA:27490 |
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fused heptose 7-phosphate kinase/heptose 1-phosphate adenyltransferaseMetaCyc:CPLX0-3661 | catalyzes | D-glycero-beta-D-manno-heptose 7-phosphate + ATP => D-glycero-beta-D-manno-heptose 1,7-bisphosphate + ADP + H(+)RHEA:27474 |
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D-glycero-beta-D-manno-heptose-1,7-bisphosphate 7-phosphataseUniProtKB:P63228 | catalyzes | D-glycero-beta-D-manno-heptose 1,7-bisphosphate + H2O => D-glycero-beta-D-manno-heptose 1-phosphate + phosphateRHEA:28519 |
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fused heptose 7-phosphate kinase/heptose 1-phosphate adenyltransferaseMetaCyc:CPLX0-3661 | catalyzes | D-glycero-beta-D-manno-heptose 1-phosphate + ATP + H(+) => ADP-D-glycero-beta-D-manno-heptose + diphosphateRHEA:27466 |
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ADP-L-glycero-D-mannoheptose 6-epimeraseMetaCyc:CPLX0-3681 | catalyzes The selected biosynthetic direction does not assert irreversible chemistry. | ADP-D-glycero-beta-D-manno-heptose => ADP-L-glycero-beta-D-manno-heptoseRHEA:17578 |
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Phosphoheptose isomeraseUniProtKB:P63224 | part_of The native complex contains 4 identical subunits; the protein node is not independently assigned monomeric catalytic sufficiency. | D-sedoheptulose 7-phosphate isomeraseMetaCyc:CPLX0-7660 |
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Bifunctional protein HldEUniProtKB:P76658 | part_of The native complex contains 2 identical subunits; the protein node is not independently assigned monomeric catalytic sufficiency. | fused heptose 7-phosphate kinase/heptose 1-phosphate adenyltransferaseMetaCyc:CPLX0-3661 |
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ADP-L-glycero-D-manno-heptose-6-epimeraseUniProtKB:P67910 | part_of The native complex contains 5 identical subunits; the protein node is not independently assigned monomeric catalytic sufficiency. | ADP-L-glycero-D-mannoheptose 6-epimeraseMetaCyc:CPLX0-3681 |
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D-sedoheptulose 7-phosphate isomeraseMetaCyc:CPLX0-7660 | has_cofactor Similarity-based cofactor annotation is retained with its evidence grade; no direct K-12 zinc requirement is inferred. | zinc(2+)CHEBI:29105 |
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D-glycero-beta-D-manno-heptose-1,7-bisphosphate 7-phosphataseUniProtKB:P63228 | has_cofactor Catalytic divalent-metal alternatives are not simultaneous required occupancy. Dominant in vivo metal is not established by these annotations. | magnesium(2+)CHEBI:18420 |
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D-glycero-beta-D-manno-heptose-1,7-bisphosphate 7-phosphataseUniProtKB:P63228 | has_cofactor Catalytic divalent-metal alternatives are not simultaneous required occupancy. Dominant in vivo metal is not established by these annotations. | manganese(2+)CHEBI:29035 |
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D-glycero-beta-D-manno-heptose-1,7-bisphosphate 7-phosphataseUniProtKB:P63228 | has_cofactor Catalytic divalent-metal alternatives are not simultaneous required occupancy. Dominant in vivo metal is not established by these annotations. | cobalt(2+)CHEBI:48828 |
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D-glycero-beta-D-manno-heptose-1,7-bisphosphate 7-phosphataseUniProtKB:P63228 | has_cofactor This bound Zn site is distinct from catalytic Mg. No universal Zn requirement or established physiological regulatory role is asserted. | zinc(2+)CHEBI:29105 |
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ADP-L-glycero-D-mannoheptose 6-epimeraseMetaCyc:CPLX0-3681 | has_cofactor NADP is the physiological bound cofactor; NAD is an alternative with lower activity. Neither is consumed in the balanced net epimerization. | NADP(3-)CHEBI:58349 |
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ADP-L-glycero-D-mannoheptose 6-epimeraseMetaCyc:CPLX0-3681 | has_cofactor NADP is the physiological bound cofactor; NAD is an alternative with lower activity. Neither is consumed in the balanced net epimerization. | NAD(1-)CHEBI:57540 |
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2 D-sedoheptulose 7-phosphate => D-glycero-alpha-D-manno-heptose 7-phosphate + D-glycero-beta-D-manno-heptose 7-phosphateRHEA:27490 | part_of | MetaCyc:PWY0-1241 |
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D-glycero-beta-D-manno-heptose 7-phosphate + ATP => D-glycero-beta-D-manno-heptose 1,7-bisphosphate + ADP + H(+)RHEA:27474 | part_of | MetaCyc:PWY0-1241 |
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D-glycero-beta-D-manno-heptose 1,7-bisphosphate + H2O => D-glycero-beta-D-manno-heptose 1-phosphate + phosphateRHEA:28519 | part_of | MetaCyc:PWY0-1241 |
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D-glycero-beta-D-manno-heptose 1-phosphate + ATP + H(+) => ADP-D-glycero-beta-D-manno-heptose + diphosphateRHEA:27466 | part_of | MetaCyc:PWY0-1241 |
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ADP-D-glycero-beta-D-manno-heptose => ADP-L-glycero-beta-D-manno-heptoseRHEA:17578 | part_of | MetaCyc:PWY0-1241 |
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2 D-sedoheptulose 7-phosphate => D-glycero-alpha-D-manno-heptose 7-phosphate + D-glycero-beta-D-manno-heptose 7-phosphateRHEA:27490 | provides_input_for A shared chemical and native predecessor relation establish this sequence; no physical channeling or obligatory enzyme complex is inferred. | D-glycero-beta-D-manno-heptose 7-phosphate + ATP => D-glycero-beta-D-manno-heptose 1,7-bisphosphate + ADP + H(+)RHEA:27474 |
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D-glycero-beta-D-manno-heptose 7-phosphate + ATP => D-glycero-beta-D-manno-heptose 1,7-bisphosphate + ADP + H(+)RHEA:27474 | provides_input_for A shared chemical and native predecessor relation establish this sequence; no physical channeling or obligatory enzyme complex is inferred. | D-glycero-beta-D-manno-heptose 1,7-bisphosphate + H2O => D-glycero-beta-D-manno-heptose 1-phosphate + phosphateRHEA:28519 |
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D-glycero-beta-D-manno-heptose 1,7-bisphosphate + H2O => D-glycero-beta-D-manno-heptose 1-phosphate + phosphateRHEA:28519 | provides_input_for A shared chemical and native predecessor relation establish this sequence; no physical channeling or obligatory enzyme complex is inferred. | D-glycero-beta-D-manno-heptose 1-phosphate + ATP + H(+) => ADP-D-glycero-beta-D-manno-heptose + diphosphateRHEA:27466 |
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D-glycero-beta-D-manno-heptose 1-phosphate + ATP + H(+) => ADP-D-glycero-beta-D-manno-heptose + diphosphateRHEA:27466 | provides_input_for A shared chemical and native predecessor relation establish this sequence; no physical channeling or obligatory enzyme complex is inferred. | ADP-D-glycero-beta-D-manno-heptose => ADP-L-glycero-beta-D-manno-heptoseRHEA:17578 |
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References
MetaCyc:5.1.3.20-RXN5.1.3.20-RXN (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:CPLX0-3661fused heptose 7-phosphate kinase/heptose 1-phosphate adenyltransferase (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:CPLX0-3681ADP-L-glycero-D-mannoheptose 6-epimerase (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:CPLX0-7660D-sedoheptulose 7-phosphate isomerase (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:EG10838-MONOMEREG10838-MONOMER (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:G6106-MONOMERG6106-MONOMER (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:G7590-MONOMERG7590-MONOMER (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:PWY0-1241ADP-L-glycero-beta-D-manno-heptose biosynthesis (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:RXN0-4301RXN0-4301 (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:RXN0-4341RXN0-4341 (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:RXN0-4342RXN0-4342 (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)MetaCyc:RXN0-4361RXN0-4361 (source version: MetaCyc 22.5; complete native XML retrieved 2026-10-11 UTC)PMID:10896473The crystal structure of ADP-L-glycero-D-mannoheptose 6-epimerase: catalysis with a twist. (source version: 2000; Europe PMC indexed primary abstract; digest covers complete core XML response, not full article retrieved 2026-10-11 UTC)PMID:11313358Evidence that NADP+ is the physiological cofactor of ADP-L-glycero-D-mannoheptose 6-epimerase. (source version: 2001; Europe PMC indexed primary abstract; digest covers complete core XML response, not full article retrieved 2026-10-11 UTC)PMID:11751812Biosynthesis pathway of ADP-L-glycero-beta-D-manno-heptose in Escherichia coli. (source version: 2002; complete primary article HTML/BioC response; exact response bytes retrieved 2026-10-11 UTC)PMID:16030223Functional analysis of the glycero-manno-heptose 7-phosphate kinase domain from the bifunctional HldE protein, which is involved in ADP-L-glycero-D-manno-heptose biosynthesis. (source version: 2005; Europe PMC indexed primary abstract; digest covers complete core XML response, not full article retrieved 2026-10-11 UTC)PMID:17316025A two-base mechanism for Escherichia coli ADP-L-glycero-D-manno-heptose 6-epimerase. (source version: 2007; Europe PMC indexed primary abstract; digest covers complete core XML response, not full article retrieved 2026-10-11 UTC)PMID:18056714Structure and function of sedoheptulose-7-phosphate isomerase, a critical enzyme for lipopolysaccharide biosynthesis and a target for antibiotic adjuvants. (source version: 2008; Europe PMC indexed primary abstract; digest covers complete core XML response, not full article retrieved 2026-10-11 UTC)PMID:20050614Structural determinants of substrate recognition in the HAD superfamily member D-glycero-D-manno-heptose-1,7-bisphosphate phosphatase (GmhB) . (source version: 2010; complete primary article HTML/BioC response; exact response bytes retrieved 2026-10-11 UTC)PMID:20050615Divergence of biochemical function in the HAD superfamily: D-glycero-D-manno-heptose-1,7-bisphosphate phosphatase (GmhB). (source version: 2010; complete primary article HTML/BioC response; exact response bytes retrieved 2026-10-11 UTC)PMID:7929099Purification and properties of the Escherichia coli K-12 NAD-dependent nucleotide diphosphosugar epimerase, ADP-L-glycero-D-mannoheptose 6-epimerase. (source version: 1994; Europe PMC indexed primary abstract; digest covers complete core XML response, not full article retrieved 2026-10-11 UTC)RHEA:17578Rhea directional reaction 17578 (source version: Rhea 142, 2026-09-02; digest covers complete compressed RDF, with exact reaction and side locators in evidence)RHEA:27466Rhea directional reaction 27466 (source version: Rhea 142, 2026-09-02; digest covers complete compressed RDF, with exact reaction and side locators in evidence)RHEA:27474Rhea directional reaction 27474 (source version: Rhea 142, 2026-09-02; digest covers complete compressed RDF, with exact reaction and side locators in evidence)RHEA:27490Rhea directional reaction 27490 (source version: Rhea 142, 2026-09-02; digest covers complete compressed RDF, with exact reaction and side locators in evidence)RHEA:28519Rhea directional reaction 28519 (source version: Rhea 142, 2026-09-02; digest covers complete compressed RDF, with exact reaction and side locators in evidence)UniProtKB:P63224Phosphoheptose isomerase (source version: UniProt 2026_03, released 2026-09-02; complete reviewed JSON retrieved 2026-10-11 UTC)UniProtKB:P63228D-glycero-beta-D-manno-heptose-1,7-bisphosphate 7-phosphatase (source version: UniProt 2026_03, released 2026-09-02; complete reviewed JSON retrieved 2026-10-11 UTC)UniProtKB:P67910ADP-L-glycero-D-manno-heptose-6-epimerase (source version: UniProt 2026_03, released 2026-09-02; complete reviewed JSON retrieved 2026-10-11 UTC)UniProtKB:P76658Bifunctional protein HldE (source version: UniProt 2026_03, released 2026-09-02; complete reviewed JSON retrieved 2026-10-11 UTC)
Curation history
- Codex
- CREATE — Add the complete five-reaction ADP-heptose pathway.
Resolved GmhA identity against native and current authorities, preserved both formal GmhA anomers and all five steps, and distinguished enzyme assemblies, catalytic metal alternatives, structural zinc and recycled NADP. Source and duplicate-search dossiers are in research/pathway_additions/2026-10-11-nicotine-next; shared authorities, generated pages, final gates and independent reviews are recorded separately.
- CREATE — Add the complete five-reaction ADP-heptose pathway.