QueE is the cytoplasmic radical S-adenosyl-L-methionine enzyme 7-carboxy-7-deazaguanine (CDG) synthase. Using a single [4Fe-4S] cluster that binds and reductively cleaves SAM, and a catalytic Mg2+ ion, it catalyses the radical-mediated ring contraction of 6-carboxy-5,6,7,8-tetrahydropterin (made by QueD) to CDG with release of ammonium. CDG is converted by QueC to 7-cyano-7-deazaguanine (preQ0), the precursor of the queuosine modification at the wobble position of tRNAs Asp, Asn, His and Tyr; queE deletion mutants lack queuosine-modified tRNA. E. coli QueE forms a head-to-tail homodimer and is reduced physiologically by flavodoxin. QueE also has a second, catalysis-independent role: when strongly induced by the PhoQ/PhoP two-component system (for example by cationic antimicrobial peptides or low Mg2+), it localizes to the FtsZ ring and blocks septation, causing filamentous growth. The two functions are separable by mutation.
Definition: Catalysis of the reaction: 6-carboxy-5,6,7,8-tetrahydropterin + H+ = 7-carboxy-7-deazaguanine + NH4+. The reaction is a radical S-adenosyl-L-methionine-initiated ring contraction of the pterin to the pyrrolopyrimidine core of 7-deazapurines, and requires a Mg2+ ion.
Justification: This is the activity of QueE (EC 4.3.99.3, RHEA:27974), the step that creates the 7-deazapurine core of queuosine, archaeosine and deazapurine antibiotics. GO has no matching term: QuickGO searches for "7-carboxy-7-deazaguanine synthase", "carbaguanine" and "CDG synthase", and an OLS cross-reference search for RHEA:27974 (checked 2026-10-19), return nothing, so QueE is annotated only to the general GO:0016840 carbon-nitrogen lyase activity.
Parent term: carbon-nitrogen lyase activity
Mappings:
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | IEA GO_REF:0000104 | KEEP AS NON CORE | Summary: QueE enzymes require a catalytic Mg2+ ion bound in the active site, separate from the [4Fe-4S] cluster. Reason: This is a separate metal ion, so it is kept (the RADICAL_SAM treatment rule keeps metal-ion terms only for a separate metal). Mg2+ dependence is shown for QueE homologs and the binding site is conserved, but the E. coli structure was solved without Mg2+ bound, so the claim for P64554 rests on homology. It is a cofactor-binding property of the core reaction rather than a separate function. Supporting Evidence: PMID:30341796 All QueE homologs tested require Mg 2+ for catalysis PMID:30341796 Finally, the binding site for the required Mg 2+ ion appears to be conserved. |
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: Root catalytic-activity term from the radical SAM InterPro signature. QueE has a known specific reaction, CPH4 to CDG (RHEA:27974, EC 4.3.99.3). Reason: Per the RADICAL_SAM treatment rule, replaced by the specific reaction. GO has no term for CDG synthase (QuickGO searches for "7-carboxy-7-deazaguanine synthase", "carbaguanine", "CDG synthase" and an OLS xref search for RHEA:27974 return nothing), so the replacement is the new term requested in proposed_new_terms. Proposed replacements: 7-carboxy-7-deazaguanine synthase activity (6-carboxy-5,6,7,8-tetrahydropterin to 7-carboxy-7-deazaguanine) Supporting Evidence: PMID:19354300 The above observations are consistent with the formation of 7-carboxy-7-deazaguanine (CDG) as the product of QueE. file:ECOLI/queE/queE-uniprot.txt Reaction=6-carboxy-5,6,7,8-tetrahydropterin + H(+) = 7-carboxy-7- |
| GO:0005829 cytosol | IDA PMID:18304323 Protein abundance profiling of the Escherichia coli cytosol. | ACCEPT | Summary: Detected in the E. coli cytosolic proteome. Reason: QueE is a soluble cytoplasmic enzyme with no signal peptide or transmembrane segment; fluorescent fusions show diffuse cytoplasmic signal. The gene name is not in the parsed text of this proteomics paper (it is presumably in supplementary tables), so I defer to the curator. Supporting Evidence: PMID:27471053 The YFP-QueE localization in cell filaments is always observed on top of considerable diffuse cytoplasmic YFP-QueE fluorescence. |
| GO:0005829 cytosol | IDA PMID:27471053 Antimicrobial peptides trigger a division block in Escherich... | ACCEPT | Summary: YFP-QueE shows diffuse cytoplasmic fluorescence, with an additional Z-ring pool when highly expressed. Reason: Direct imaging of a functional fusion; the cytosol is where the biosynthetic activity operates. Supporting Evidence: PMID:27471053 The YFP-QueE localization in cell filaments is always observed on top of considerable diffuse cytoplasmic YFP-QueE fluorescence. |
| GO:0008616 tRNA queuosine(34) biosynthetic process | IBA GO_REF:0000033 | MODIFY | Summary: QueE catalyses a step of de novo queuosine synthesis (CPH4 to CDG, upstream of preQ0). Reason: The claim is correct (QueE does a step of the pathway, so the participation test is met), but GO:0008616 also covers salvage of queuine. E. coli makes queuosine de novo from GTP, which is the child term GO:0160253. The IBA node placement is not disputed; the target appears among its own sources because it has experimental grounding. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000881343 · PTN000881343 SUPPORTS TRANSFER Node placement is sound; the transferred process term is simply broader than the de novo child the QueE clade supports. Proposed replacements: de novo tRNA queuosine(34) biosynthetic process Supporting Evidence: PMID:38768229 confirming that QueE is required to produce Q |
| GO:0008616 tRNA queuosine(34) biosynthetic process | IEA GO_REF:0000104 | MODIFY | Summary: Same claim as the IBA row. Reason: Correct but general; refined to the de novo child term GO:0160253, as for the IBA row. Proposed replacements: de novo tRNA queuosine(34) biosynthetic process Supporting Evidence: PMID:27471053 QueE catalyses the formation of 7-carboxy-7-deazaguanine (CDG), which is an intermediate in the biosynthesis of queuosine |
| GO:0008616 tRNA queuosine(34) biosynthetic process | IMP PMID:21502530 Discovery of epoxyqueuosine (oQ) reductase reveals parallels... | MODIFY | Summary: LC-MS screen of the Keio single-gene knockout collection for queuosine pathway genes; the queE knockout lacks queuosine. Reason: Abstract-only cache; the queE result is presumably in the full text, and it is independently confirmed by APB-gel northern blots of a queE deletion (PMID:38768229). The claim is right but refined to the de novo child term GO:0160253, consistent with the other rows. Proposed replacements: de novo tRNA queuosine(34) biosynthetic process Supporting Evidence: PMID:21502530 we have screened 1,755 single gene knockouts of Escherichia coli and have identified the key final step in the biosynthesis of Q PMID:38768229 confirming that QueE is required to produce Q |
| GO:0016840 carbon-nitrogen lyase activity | IBA GO_REF:0000033 | MODIFY | Summary: CDG synthase eliminates ammonium from CPH4 while contracting the ring, a carbon-nitrogen lyase reaction (EC 4.3.99.3). Reason: Correct, and the most specific existing GO term; the IBA node (seeded by B. subtilis QueE, O31677, which carries an IDA for this term) is well placed. But the specific reaction lacks a GO term, so the replacement is the requested new child term, with GO:0016840 as its proposed parent. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000881343 · PTN000881343 SUPPORTS TRANSFER Sound node, seeded by B. subtilis QueE (O31677) IDA; the only problem is that GO lacks a term for the specific CDG synthase reaction. Proposed replacements: 7-carboxy-7-deazaguanine synthase activity (6-carboxy-5,6,7,8-tetrahydropterin to 7-carboxy-7-deazaguanine) Supporting Evidence: PMID:19354300 The above observations are consistent with the formation of 7-carboxy-7-deazaguanine (CDG) as the product of QueE. |
| GO:0016840 carbon-nitrogen lyase activity | IEA GO_REF:0000104 | MODIFY | Summary: Same claim as the IBA row. Reason: As for the IBA row; refined to the requested CDG synthase term. Proposed replacements: 7-carboxy-7-deazaguanine synthase activity (6-carboxy-5,6,7,8-tetrahydropterin to 7-carboxy-7-deazaguanine) Supporting Evidence: file:ECOLI/queE/queE-uniprot.txt Reaction=6-carboxy-5,6,7,8-tetrahydropterin + H(+) = 7-carboxy-7- |
| GO:0032153 cell division site | IDA PMID:27471053 Antimicrobial peptides trigger a division block in Escherich... | KEEP AS NON CORE | Summary: Under filamenting conditions (PhoQ/PhoP activation or overexpression), YFP-QueE co-localizes with FtsZ rings. Reason: Directly observed, and linked to the moonlighting division-inhibitor role, but it is a conditional pool seen at high QueE levels and not where the biosynthetic activity acts. Supporting Evidence: PMID:27471053 Imaging of cells expressing a functional YFP-QueE fusion indicates that under filamenting conditions QueE localizes to the divisome, suggesting that the protein interacts directly with division machinery. PMID:38768229 When cellular QueE levels are high, it co-localizes with the central cell division protein FtsZ at the septal site, blocking division and resulting in filamentous growth. |
| GO:0032466 negative regulation of cytokinesis | IMP PMID:27471053 Antimicrobial peptides trigger a division block in Escherich... | MODIFY | Summary: QueE induced by PhoQ/PhoP signalling blocks septation; deletion of queE suppresses the division block of mgrB mutants. The effect does not depend on queuosine synthesis. Reason: The function is real and specific to QueE itself (it localizes to the divisome and separable point mutants affect only this role, PMID:38768229), but the block is at septation downstream of Z-ring formation, so the bacterial is_a descendant GO:0010974 negative regulation of division septum assembly is more precise. Non-core relative to CDG synthesis. Proposed replacements: negative regulation of division septum assembly Supporting Evidence: PMID:27471053 These results indicate that filaments have a continuous cytoplasm and therefore the block in cell division is due to inhibition of septation. PMID:27471053 However, QueE's effect on cell division is independent of the queuosine biosynthesis pathway. PMID:38768229 Interestingly, one of the mutants, QueE R27A, abolished Q-tRNA formation but retained the ability to cause filamentation like the WT |
| GO:0051536 iron-sulfur cluster binding | IEA GO_REF:0000002 | MODIFY | Summary: Correct but general; the QueE cluster is a [4Fe-4S] radical SAM cluster. Reason: Per the RADICAL_SAM treatment rule, refined to GO:0051539, which the gene already carries. Proposed replacements: 4 iron, 4 sulfur cluster binding Supporting Evidence: file:ECOLI/queE/queE-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 | IEA GO_REF:0000104 | ACCEPT | Summary: QueE binds one radical SAM [4Fe-4S] cluster through the CX3CX2C motif (Cys31, Cys35, Cys38). Reason: Catalytic cofactor of an active radical SAM enzyme, core per the RADICAL_SAM treatment rule. In E. coli, alanine substitution of the third cluster cysteine (C38A) abolishes Q-tRNA formation. Supporting Evidence: file:ECOLI/queE/queE-uniprot.txt Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine. PMID:38768229 The C38A mutation also prevents Q-tRNA formation |
| GO:1904047 S-adenosyl-L-methionine binding | IEA GO_REF:0000104 | ACCEPT | Summary: SAM binds the unique iron of the radical SAM cluster and is cleaved to initiate the ring contraction. Reason: Cosubstrate binding, true of every active radical SAM enzyme (RADICAL_SAM treatment rule). QueE turnover requires SAM and a reductant. Supporting Evidence: PMID:19354300 The conversion of CPH4 to this new product occurred only in the presence of SAM and dithionite |
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Download this section (compressed HTML)Q: Which divisome component does QueE contact to block septation, and why does the division block require the E45-W67 region that is absent from Pseudomonas and Bacillus QueE?
Q: Is the moonlighting division-inhibitor role of QueE worth capturing in GO-CAM as a separate activity of the same gene product, distinct from its CDG synthase activity?
Experiment: Bacterial two-hybrid and in vivo crosslinking of wild-type QueE and the division-defective E45-W67 deletion against late divisome proteins (FtsQ, FtsL, FtsB, FtsW, FtsI, FtsN), with the suppressor alleles ftsA-N170S and ftsZ-D234G as controls.
Hypothesis: QueE inhibits septation by binding a late divisome protein downstream of FtsA/FtsZ.
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