EpmB (formerly YjeK) is a cytoplasmic radical S-adenosyl-L-methionine (SAM) enzyme of the KamA lysine 2,3-aminomutase family. Using a [4Fe-4S] cluster and pyridoxal 5'-phosphate, it moves the alpha-amino group of L-lysine to C3, forming (R)-beta-lysine, the opposite enantiomer to the (S)-beta-lysine made by the clostridial enzyme in lysine fermentation. Its turnover is slow (about 0.1% of the clostridial enzyme). (R)-beta-lysine is the donor that the lysyl-tRNA synthetase paralog EpmA attaches to Lys34 of translation elongation factor P (EF-P), after which EpmC hydroxylates the modified residue. The beta-lysylated EF-P is the active form that relieves ribosome stalling at polyproline stretches, and loss of EpmB, like loss of EpmA, causes pleiotropic stress and virulence defects in Salmonella.
Definition: Catalysis of the reaction: L-lysine = (3R)-3,6-diaminohexanoate (D-beta-lysine). A radical SAM, pyridoxal 5'-phosphate-dependent migration of the alpha-amino group to C3 that gives the (R) product.
Justification: This is the activity of E. coli EpmB (RHEA:44148). The existing GO:0050066 L-lysine 2,3-aminomutase activity is defined as forming the (3S) product made by the clostridial enzyme, so it does not describe EpmB, whose (R) product is the one EpmA uses on EF-P. Rhea lists no GO term for RHEA:44148 (checked 2026-10-19).
Parent term: intramolecular aminotransferase activity
Mappings:
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: Catalytic activity, from the radical SAM domain (IPR007197). Reason: Per the RADICAL_SAM treatment rule, the root term is replaced by the specific reaction. EpmB converts L-lysine to (R)-beta-lysine (PMID:17042480). GO has no term for that stereochemistry (GO:0050066 is defined with the (3S) product), so the replacement is the proposed new term. Proposed replacements: L-lysine 2,3-aminomutase ((R)-beta-lysine-forming) activity Supporting Evidence: PMID:17042480 The product of the E. coli enzyme is (R)-beta-lysine, the enantiomer of the clostridial product. file:ECOLI/epmB/epmB-uniprot.txt Belongs to the radical SAM superfamily. KamA family. |
| GO:0016869 intramolecular aminotransferase activity | IBA GO_REF:0000033 | MODIFY | Summary: Intramolecular aminotransferase activity: EpmB moves the alpha-amino group of L-lysine to C3, making (R)-beta-lysine (PMID:17042480). Reason: Correct but general. The specific reaction is L-lysine = (R)-beta-lysine (RHEA:44148). The existing child GO:0050066 L-lysine 2,3-aminomutase activity is defined as forming (3S)-3,6-diaminohexanoate, the clostridial product, and must not be used: E. coli EpmB makes the opposite enantiomer, and only (R)-beta-lysine is the substrate EpmA uses on EF-P (PMID:21841797). The replacement is the proposed (R)-forming term, a child of this term. This refines the PAINT node rather than challenging it: GO:0016869 is right for the whole KamA family, whose members make either enantiomer. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000776770 Β· KamA-family ancestral node (PTHR30538) SUPPORTS TRANSFER The node's IBD rows assert GO:0016869 and GO:0051539 for the bacterial KamA clade, which is correct at that level: family members form either beta-lysine enantiomer, so the general parent is the right node-level claim. This MODIFY refines the term for this gene rather than challenging the node placement. The family review (interpro/panther/PTHR30538/PTHR30538-review.yaml) assesses both rows as SOUND and records that the node must not be refined to GO:0050066 family-wide. UniProtKB:P39280 Β· EpmB (this gene) as an IBD seed SUPPORTS TRANSFER EpmB appears in its own WITH/FROM because its experimental annotation is one of the descendant evidences the PAINT curator used to place the node. That is expected, and marks experimental grounding on the target itself rather than circularity. Proposed replacements: L-lysine 2,3-aminomutase ((R)-beta-lysine-forming) activity Supporting Evidence: PMID:17042480 The product of the E. coli enzyme is (R)-beta-lysine, the enantiomer of the clostridial product. file:ECOLI/epmB/epmB-uniprot.txt Reaction=L-lysine = D-beta-lysine PMID:21841797 EF-P was efficiently functionally modified with (R)-Ξ²-lysine but not (S)-Ξ²-lysine or genetically encoded Ξ±-amino acids |
| GO:0016869 intramolecular aminotransferase activity | IDA PMID:17042480 Enantiomeric free radicals and enzymatic control of stereoch... | MODIFY | Summary: Intramolecular aminotransferase activity: EpmB moves the alpha-amino group of L-lysine to C3, making (R)-beta-lysine (PMID:17042480). Reason: Correct but general. The specific reaction is L-lysine = (R)-beta-lysine (RHEA:44148). The existing child GO:0050066 L-lysine 2,3-aminomutase activity is defined as forming (3S)-3,6-diaminohexanoate, the clostridial product, and must not be used: E. coli EpmB makes the opposite enantiomer, and only (R)-beta-lysine is the substrate EpmA uses on EF-P (PMID:21841797). The replacement is the proposed (R)-forming term, a child of this term. Proposed replacements: L-lysine 2,3-aminomutase ((R)-beta-lysine-forming) activity Supporting Evidence: PMID:17042480 The product of the E. coli enzyme is (R)-beta-lysine, the enantiomer of the clostridial product. file:ECOLI/epmB/epmB-uniprot.txt Reaction=L-lysine = D-beta-lysine PMID:21841797 EF-P was efficiently functionally modified with (R)-Ξ²-lysine but not (S)-Ξ²-lysine or genetically encoded Ξ±-amino acids |
| GO:0043687 post-translational protein modification | RCA PMID:20070887 Predicting the pathway involved in post-translational modifi... | MARK AS OVER ANNOTATED | Summary: Post-translational protein modification, from the comparative-genomics prediction that YjeK and YjeA modify EF-P (PMID:20070887); later confirmed: both are needed for beta-lysyl-EF-P (PMID:22128152). Reason: EpmB is required for EF-P beta-lysylation, but it does not perform the covalent step: it makes free (R)-beta-lysine, which EpmA then ligates to EF-P Lys34 (PMID:21841797), and EpmC hydroxylates it. Requirement as the donor's supplier is necessity, not participation in modifying the protein. Comparator check (QuickGO): EpmA and EpmC carry GO:0043687, whereas biotin synthase BioB carries biotin biosynthetic process but not protein biotinylation. The term is not false in spirit, since EpmB serves only this pathway, so it is marked over-annotated rather than removed. Supporting Evidence: PMID:22128152 indicating that both enzymes, YjeA and YjeK, are required for Ξ²-lysylation of EF-P PMID:21841797 EF-P was efficiently functionally modified with (R)-Ξ²-lysine but not (S)-Ξ²-lysine or genetically encoded Ξ±-amino acids PMID:20070887 we predict that the YjeA and YjeK families of proteins are involved in EF-P modification in a subset of bacterial species |
| GO:0051536 iron-sulfur cluster binding | IEA GO_REF:0000002 | MODIFY | Summary: Iron-sulfur cluster binding, from the radical SAM domain (IPR007197). Reason: Correct but general; EpmB binds one radical SAM [4Fe-4S] cluster, so the child GO:0051539, which EpmB already carries by IDA and IBA, is the right term. Proposed replacements: 4 iron, 4 sulfur cluster binding Supporting Evidence: file:ECOLI/epmB/epmB-uniprot.txt Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine. |
| GO:0051539 4 iron, 4 sulfur cluster binding | IBA GO_REF:0000033 | ACCEPT | Summary: EpmB binds one radical SAM [4Fe-4S] cluster through three cysteines, with SAM at the exchangeable site (PMID:17042480). Reason: The radical SAM cluster is the catalytic cofactor that generates the 5'-deoxyadenosyl radical seen in EpmB turnover, so it is core. The IBA agrees with the IDA. Supporting Evidence: file:ECOLI/epmB/epmB-uniprot.txt Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine. PMID:17042480 hydrogen transfer from C2 of (S)-beta-lysine to the 5'-deoxyadenosyl radical |
| GO:0051539 4 iron, 4 sulfur cluster binding | IDA PMID:17042480 Enantiomeric free radicals and enzymatic control of stereoch... | ACCEPT | Summary: EpmB binds one radical SAM [4Fe-4S] cluster through three cysteines, with SAM at the exchangeable site (PMID:17042480). Reason: The radical SAM cluster is the catalytic cofactor that generates the 5'-deoxyadenosyl radical seen in EpmB turnover, so it is core. The IBA agrees with the IDA. Supporting Evidence: file:ECOLI/epmB/epmB-uniprot.txt Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine. PMID:17042480 hydrogen transfer from C2 of (S)-beta-lysine to the 5'-deoxyadenosyl radical |
| GO:1904047 S-adenosyl-L-methionine binding | IC PMID:17042480 Enantiomeric free radicals and enzymatic control of stereoch... | NEW | Summary: EpmB binds SAM at the unique iron of its [4Fe-4S] cluster and cleaves it to the 5'-deoxyadenosyl radical used in turnover (PMID:17042480). Reason: GOA has no SAM-binding row. Radical catalysis by EpmB is established (substrate radicals by EPR, hydrogen transfer to the 5'-deoxyadenosyl radical), and that radical can come only from SAM bound to the cluster, so SAM binding is inferred by curator from that evidence. This is a molecular function of EpmB itself. Matches the RADICAL_SAM convention for members with established catalysis. Supporting Evidence: PMID:17042480 hydrogen transfer from C2 of (S)-beta-lysine to the 5'-deoxyadenosyl radical file:ECOLI/epmB/epmB-uniprot.txt Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine. |
| GO:0030170 pyridoxal phosphate binding | IDA PMID:17042480 Enantiomeric free radicals and enzymatic control of stereoch... | NEW | Summary: EpmB requires pyridoxal 5'-phosphate, which carries the lysine amino group during the 2,3 migration (UniProt cofactor, ECO:0000269 PubMed:17042480). Reason: PLP is the second cofactor of KamA-family aminomutases; UniProt records it for EpmB from the Behshad study (experimental evidence), and Lys332 is the predicted PLP-binding lysine. The cached paper is abstract-only, so the curated UniProt cofactor line is quoted. This is the enzyme's own function, not a process inference. Supporting Evidence: file:ECOLI/epmB/epmB-uniprot.txt Name=pyridoxal 5'-phosphate file:ECOLI/epmB/epmB-uniprot.txt Belongs to the radical SAM superfamily. KamA family. |
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Download this section (compressed HTML)Q: Should GO add a beta-lysine biosynthetic process term, so that EpmB can be given its own process rather than the EF-P modification term, which belongs to EpmA and EpmC?
Q: How does the EpmB active site impose (R) rather than (S) stereochemistry, given the shared KamA fold with the clostridial enzyme?
Experiment: Solve an EpmB structure with lysine bound, swap candidate residues with those of the clostridial enzyme, and measure the product enantiomer by chiral chromatography.
Hypothesis: A few active-site residues set the (R) product stereochemistry.
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