ahpD

Summary: AhpD self-associates in its characterized oligomeric structure.

Reason: The original self-binding claim is resolved by curated homotrimer structure, rather than retained as generic protein binding. Oligomerization does not prove fixed stoichiometry for the entire four-enzyme relay.

Proposed replacements: identical protein binding

Summary: AhpD directly engages the enzyme AhpC during disulfide exchange.

Reason: PMID:15178486 maps a catalytic mixed disulfide between the partners. Enzyme binding is the precise partner-class claim; its artificial upstream donor system remains explicitly distinguished from the native relay.

Proposed replacements: enzyme binding

Summary: AhpD supplies reducing equivalents in the cytosolic AhpC relay.

Reason: The curated bacterial reactions place this soluble redox enzyme in cytosol. An R-HSA identifier denotes the host-pathway record, not that the participating bacterial AhpD is a human protein.

Summary: AhpD supplies reducing equivalents in the cytosolic AhpC relay.

Reason: The curated bacterial reactions place this soluble redox enzyme in cytosol. An R-HSA identifier denotes the host-pathway record, not that the participating bacterial AhpD is a human protein.

Summary: Membrane-fraction detection of AhpD remains source-limited.

Reason: The native H37Rv fractionation study is relevant, but target peptides and fractionation controls are not available in its abstract. The accessible record cannot resolve a peripheral membrane pool versus carryover; neither is excluded merely by soluble redox chemistry.

Summary: AhpD performs a reductive step in peroxide defense.

Reason: Direct AhpC-regeneration chemistry and its independently measured weak peroxide turnover support participation in oxidative-stress defense. This is not an assertion that the named relay is the only native defense.

Summary: AhpD reduces the oxidized active-site disulfide of AhpC.

Reason: The target-specific mixed-disulfide experiments establish thiol-disulfide exchange, consistent with the PAINT ancestral assertion. The 2004 assay uses bovine DHLDH/free lipoamide upstream; the direct AhpC–AhpD step remains target-specific.

Summary: AhpD reduces the oxidized active-site disulfide of AhpC.

Reason: The target-specific mixed-disulfide experiments establish thiol-disulfide exchange, consistent with the PAINT ancestral assertion. The 2004 assay uses bovine DHLDH/free lipoamide upstream; the direct AhpC–AhpD step remains target-specific.

Summary: AhpD reduces the oxidized active-site disulfide of AhpC.

Reason: The target-specific mixed-disulfide experiments establish thiol-disulfide exchange, consistent with the PAINT ancestral assertion. The 2004 assay uses bovine DHLDH/free lipoamide upstream; the direct AhpC–AhpD step remains target-specific.

Summary: AhpD has a defined disulfide-reductase role in the antioxidant relay.

Reason: Refine the broad antioxidant annotation to the experimentally resolved disulfide oxidoreductase relay and the independently assayed weak hydroperoxide-reducing activity. The latter remains non-core and was measured with a heterologous Salmonella AhpF reducing system, not as proof of a separate native physiological route. Current GO:0051920 specifies protein-dithiol oxidation to a protein disulfide coupled to hydroperoxide reduction, not membership in a particular structural family. PMID:11914371 describes Cys133 peroxide attack followed by a Cys130–Cys133 disulfide, and PMID:12761216 tests that mechanism by mutagenesis, crystallography and kinetics. This specific chemistry supports GO:0051920 despite AhpD's distinct fold; GO:0004601 would discard supported reaction detail. The activity remains secondary to the physiological AhpC-regeneration relay.

Proposed replacements: disulfide oxidoreductase activity peroxiredoxin activity

Summary: AhpD regenerates a peroxide-reducing enzyme and thereby supports redox balance.

Reason: This protein performs an electron-transfer step, beyond binding or stress induction. The PAINT target seed and direct catalytic exchange support the homeostatic participation claim.

Summary: AhpD regenerates a peroxide-reducing enzyme and thereby supports redox balance.

Reason: This protein performs an electron-transfer step, beyond binding or stress induction. The PAINT target seed and direct catalytic exchange support the homeostatic participation claim.

Summary: Purified AhpD also exhibits weak alkylhydroperoxidase activity.

Reason: PMID:10766746 explicitly assays this secondary activity with heterologous Salmonella AhpF; it is not inferred solely from the AhpD family name. The better-established native role is AhpC regeneration. No predominance or broad substrate specificity is inferred from the secondary assay. Current GO:0051920 specifies protein-dithiol oxidation to a protein disulfide coupled to hydroperoxide reduction, not membership in a particular structural family. PMID:11914371 describes Cys133 peroxide attack followed by a Cys130–Cys133 disulfide, and PMID:12761216 tests that mechanism by mutagenesis, crystallography and kinetics. This specific chemistry supports GO:0051920 despite AhpD's distinct fold; GO:0004601 would discard supported reaction detail. The activity remains secondary to the physiological AhpC-regeneration relay.

Summary: AhpD contributes a catalytic redox step to oxidant detoxification.

Reason: Reduction of oxidized AhpC allows further peroxide turnover, and AhpD also has experimentally reported low peroxide activity. Its contribution is not a mere substrate-depletion phenotype.

Summary: AhpD contributes to the lipoyl-dependent peroxide-reduction system.

Reason: The four-protein relay supports this overall activity: AhpD transfers reducing equivalents to AhpC. The earlier isolated AhpD hydroperoxidase experiment did not itself identify the native lipoyl donor, so it is not the sole support for this donor-specific annotation. No direct NADH oxidation by AhpD is asserted.

Summary: AhpD contributes to the lipoyl-dependent peroxide-reduction system.

Reason: The four-protein relay supports this overall activity: AhpD transfers reducing equivalents to AhpC. The earlier isolated AhpD hydroperoxidase experiment did not itself identify the native lipoyl donor, so it is not the sole support for this donor-specific annotation. No direct NADH oxidation by AhpD is asserted.