LpxA is the cytosolic acyl-[acyl-carrier-protein]--UDP-N-acetylglucosamine O-acyltransferase (EC 2.3.1.129) that catalyses the first, committed step of lipid A biosynthesis: transfer of a (3R)-hydroxyacyl chain from acyl-ACP to the 3-hydroxyl of UDP-GlcNAc. It is a homotrimer built from hexapeptide repeats forming a left-handed beta-helix, whose repeat register acts as a hydrocarbon ruler. The P. aeruginosa enzyme is specific for 3-hydroxydecanoyl-ACP, over a thousand-fold over the 3-hydroxymyristoyl-ACP preferred by the Escherichia coli enzyme, which is why P. aeruginosa lipid A carries 10:0(3-OH) at positions 3 and 3'. Lipid A anchors the lipopolysaccharide in the outer membrane, so the reaction initiates both the lipid A and the lipopolysaccharide biosynthetic pathways.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | MODIFY | Summary: Correct but general; LpxA is a soluble cytosolic enzyme and the gene already carries cytosol. Reason: GO:0005829 cytosol is a part_of descendant of GO:0005737 and is already annotated here by IBA; the E. coli orthologue has cytosol by IDA. Proposed replacements: cytosol Supporting Evidence: file:PSEAE/lpxA/lpxA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: The soluble first enzyme of lipid A synthesis acts in the cytosol on UDP-GlcNAc and acyl-ACP; the E. coli seed has cytosol by IDA. Reason: Both substrates are cytosolic, the protein has no signal peptide or transmembrane segment, and the whole LpxA family under PTN000602377 shares this architecture. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P0A722 · E. coli LpxA SUPPORTS TRANSFER GO:0005829 by IDA (PMID:18304323, EcoCyc). PANTHER:PTN000602377 · PTN000602377 (PTHR43480) SUPPORTS TRANSFER LpxA family of Gram-negative bacteria; QuickGO lists 24 GO:0005829 leaf IBAs from this node on 2026-10-28. Supporting Evidence: file:PSEAE/lpxA/lpxA-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0008610 lipid biosynthetic process | IEA GO_REF:0000002 | MODIFY | Summary: Very general InterPro lipid-A-LpxA mapping; the lipid made is lipid A. Reason: GO:0009245 lipid A biosynthetic process is a descendant of GO:0008610 and is already on this gene; the LpxA-specific signatures (TIGR01852, IPR010137) support it. Proposed replacements: lipid A biosynthetic process Supporting Evidence: file:PSEAE/lpxA/lpxA-uniprot.txt DR NCBIfam; TIGR01852; lipid_A_lpxA; 1. |
| GO:0008780 acyl-[acyl-carrier-protein]-UDP-N-acetylglucosamine O-acyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function, directly demonstrated for the P. aeruginosa enzyme: it acylates UDP-GlcNAc from 3-hydroxydecanoyl-ACP. Reason: The IBD is seeded by E. coli LpxA, which has this activity by IDA, and the P. aeruginosa enzyme was assayed directly after expression cloning, with >1000-fold selectivity for 3-hydroxydecanoyl-ACP. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P0A722 · E. coli LpxA SUPPORTS TRANSFER GO:0008780 by IDA (PMID:3549716). PANTHER:PTN000602373 · PTN000602373 (PTHR43480, the activity node) SUPPORTS TRANSFER A separate, deeper node from the LPS node PTN000602377: its seeds include the Arabidopsis locus AT4G29540 as well as E. coli LpxA, so the activity is placed above the bacterial LpxA clade. The reaction is the family's defining one and is directly shown for PA3644. Supporting Evidence: PMID:9440522 Pseudomonas lpxA encodes a 10-carbon-specific UDP-GlcNAc acyltransferase, whereas the E. coli transferase is selective for a 14-carbon acyl chain. PMID:9440522 LpxA assays of extracts of this construct indicated that it is > 1,000-fold more selective for 3-hydroxydecanoyl-ACP than for 3-hydroxymyristoyl-ACP. |
| GO:0008780 acyl-[acyl-carrier-protein]-UDP-N-acetylglucosamine O-acyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Same core activity from the EC/Rhea mapping. Reason: Reinforces the IBA row; the reaction is the one assayed for the P. aeruginosa enzyme. Supporting Evidence: file:PSEAE/lpxA/lpxA-uniprot.txt a (3R)-hydroxyacyl-[ACP] + UDP-N-acetyl-alpha-D-glucosamine PMID:9440522 UDP-N-acetylglucosamine-3-O-acyltransferase (UDP-GlcNAc acyltransferase) catalyzes the first step of lipid A biosynthesis |
| GO:0009103 lipopolysaccharide biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: True for LpxA and for the clade: the enzyme makes the first intermediate of lipid A, the glycolipid anchor of LPS. The IBD's only seed is this gene's own PseudoCAP row, whose cited paper is wrong (see that row), but genuine direct evidence for the activity exists in PMID:9440522. Reason: PTHR43480 is the LpxA family and contains only Gram-negative bacteria that make lipid A, so an LPS-biosynthesis assertion suits the whole node. The target appearing in its own With/From would ordinarily mark experimental grounding on the target; here the seed reference is, by its abstract, a lipid A structural study rather than an enzyme assay, so the grounding comes from PMID:9440522 instead. The term stands; GO:0009245 lipid A biosynthetic process (not a descendant of this term) is the more mechanism-specific claim and is annotated separately. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE MISCITATION Sources checked: UniProtKB:Q9X6P4 · lpxA (self; sole IBD seed, IDA PMID:1904818) SOURCE WEAK OR INFERRED The seed's cited paper, by its abstract, assays lipid A structure, not the enzyme (full text not read); the claim is nevertheless right and is supported by PMID:9440522. PANTHER:PTN000602377 · PTN000602377 (PTHR43480) SUPPORTS TRANSFER 268 LpxA-family members, all Gram-negative; QuickGO lists 24 GO:0009103 leaf IBAs from this node on 2026-10-28, all lpxA genes. Supporting Evidence: PMID:9440522 UDP-N-acetylglucosamine-3-O-acyltransferase (UDP-GlcNAc acyltransferase) catalyzes the first step of lipid A biosynthesis file:PSEAE/lpxA/lpxA-uniprot.txt Involved in the biosynthesis of lipid A, a phosphorylated |
| GO:0009245 lipid A biosynthetic process | IEA GO_REF:0000104 | ACCEPT | Summary: Core process: LpxA performs step 1 of lipid IV(A) synthesis, and the P. aeruginosa enzyme's C10 specificity accounts for the native lipid A acylation pattern. Reason: Directly supported for this protein: expression of the cloned PAO1 lpxA in E. coli produced lipid A with 3-hydroxydecanoate at positions 3 and 3', the pattern of authentic P. aeruginosa lipid A. The E. coli orthologue carries this term by IDA. Supporting Evidence: PMID:9440522 consistent with 3-hydroxydecanoate rather than 3-hydroxymyristate at positions 3 and 3' PMID:1904818 3-hydroxydecanoic acid groups [10:0(3-OH)] at positions 3 and 3' |
| GO:0016740 transferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Root-level transferase term from the hexapeptide-repeat signature. Reason: GO:0008780 is the specific descendant, supported by EC 2.3.1.129, by the LpxA-specific signatures and by direct assay of the P. aeruginosa enzyme. Proposed replacements: acyl-[acyl-carrier-protein]-UDP-N-acetylglucosamine O-acyltransferase activity Supporting Evidence: PMID:9440522 Pseudomonas lpxA encodes a 10-carbon-specific UDP-GlcNAc acyltransferase, whereas the E. coli transferase is selective for a 14-carbon acyl chain. |
| GO:0009103 lipopolysaccharide biosynthetic process | IDA PMID:1904818 Structural characterization of the lipid A component of Pseu... | ACCEPT | Summary: The claim is correct, but the cited paper is a 1991 chemical and NMR structural analysis of P. aeruginosa lipid A whose abstract describes only structural methods on purified LPS and mentions no enzyme assay or lpxA (full text not read); the gene was cloned in 1998. The direct evidence for PA3644 is PMID:9440522. Reason: LpxA catalyses the first step of lipid A synthesis and lipid A is the LPS anchor, so involvement in LPS biosynthesis holds, and the activity was assayed directly for the cloned PAO1 enzyme in PMID:9440522 (which also shows it makes the 10:0(3-OH) pattern the cited structural paper reports). The row is kept and its reference flagged for repointing rather than removed: this is a citation defect, not a wrong claim. It is the sole seed of the GO:0009103 IBD at PTN000602377. Supporting Evidence: PMID:9440522 we here report the isolation of the lpxA gene of Pseudomonas aeruginosa PMID:9440522 A plasmid (pGD3) containing the 1.3-kb SalI-PstI fragment complemented E. coli RO138, a temperature-sensitive mutant harboring lpxA2. |
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Download this section (compressed HTML)Q: Would the GO:0009103 IBD at PTN000602377 be better stated as GO:0009245 lipid A biosynthetic process, which E. coli LpxA already carries by IDA and which names the reaction the family performs?
Experiment: Determine the structure of P. aeruginosa LpxA with 3-hydroxydecanoyl-ACP to identify the hexapeptide-repeat residues that set the C10 hydrocarbon ruler, and test chain-length specificity of ruler swap mutants in vitro and by lipid A mass spectrometry in PAO1.
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