AroQ (Rv2537c) is the type II 3-dehydroquinate dehydratase (3-dehydroquinase, EC 4.2.1.10) of Mycobacterium tuberculosis and the only 3-dehydroquinase encoded in its genome. It catalyses the third step of the shikimate (chorismate) pathway, the dehydration of 3-dehydroquinate to 3-dehydroshikimate, by a trans elimination through an enolate intermediate, with Tyr-25 abstracting the C-2 proton, His-102 protonating the leaving hydroxyl and Arg-20 stabilising the transition state. The 147-residue protein has a flavodoxin-like fold, assembles into a very heat-stable cytosolic homododecamer, and has an unusually low Km for its substrate. It is unrelated in sequence and mechanism to the type I (Schiff base) dehydroquinases of enteric bacteria but related to the catabolic dehydroquinases of the fungal quinic acid utilization pathway, and when expressed in an Aspergillus qutE mutant it can substitute for the catabolic enzyme. In M. tuberculosis its role is biosynthetic, supplying the chorismate needed for aromatic amino acids, folate, menaquinone and mycobactin, and it has been studied extensively as an antitubercular drug target, with many inhibitor-bound crystal structures.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003855 3-dehydroquinate dehydratase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from the PTHR21272 root node PTN000479790, seeded by the catabolic fungal enzymes (A. nidulans QutE, N. crassa qa-2) and by M. tuberculosis AroQ itself. Reason: The PTHR21272 family review judges this node SOUND and the activity safe family wide; biosynthetic and catabolic type II enzymes catalyse the same reaction. No PAINT loss lies on the AroQ lineage. AroQ in its own WITH/FROM marks its experimental grounding, not circularity. Supporting Evidence: PMID:10360352 the type II enzymes catalyze a trans-dehydration via an enolate intermediate. file:MYCTU/aroQ/aroQ-uniprot.txt SIMILARITY: Belongs to the type-II 3-dehydroquinase family. |
| GO:0003855 3-dehydroquinate dehydratase activity | IDA PMID:1329726 Inducible overproduction of the Aspergillus nidulans pentafu... | ACCEPT | Summary: Moore et al. (1992) overexpressed M. tuberculosis aroQ in E. coli, purified the type II 3-dehydroquinase to over 95% homogeneity and characterized it as a heat-stable homododecamer with a very low Km; the gene also restored quinate use in an A. nidulans qutE mutant. Reason: Direct assay of the purified M. tuberculosis enzyme, plus functional complementation of the fungal catabolic dehydroquinase. The paper is cached as abstract only, but the abstract itself states the purification and kinetics. Core function. Supporting Evidence: PMID:1329726 The M. tuberculosis type-II 3-dehydroquinase has been purified in bulk from overproducing strains of E. coli to greater than 95% homogeneity. PMID:1329726 The protein is extremely heat-stable, is active as a homododecamer and has the lowest reported Km value of any type-II 3-dehydroquinase. |
| GO:0003855 3-dehydroquinate dehydratase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated IEA (GO_REF:0000120) from the type II DHQase InterPro entries, EC 4.2.1.10/RHEA:21096 and the HAMAP MF_00169 UniRule. Reason: The electronic routes agree with the direct experimental evidence on this protein. Supporting Evidence: file:MYCTU/aroQ/aroQ-uniprot.txt InterPro; IPR001874; DHquinase_II. file:MYCTU/aroQ/aroQ-uniprot.txt HAMAP; MF_00169; AroQ; 1. |
| GO:0005829 cytosol | TAS Reactome:R-MTU-964851 | ACCEPT | Summary: Reactome places the AroQ-catalysed dehydration of DHQ to DHS in the cytosol. Reason: AroQ is a small soluble enzyme with no signal peptide or transmembrane segment that assembles into a cytoplasmic dodecamer; the shikimate pathway is cytosolic in bacteria. Cytosol is the appropriate specific location. Supporting Evidence: Reactome:R-MTU-964851 AroQ, which catalyzes the dehydratation of 3-dehydroquinate (DHQ) to 3-dehydroshikimate (DHS), is a type II DHQ dehydratase. file:MYCTU/aroQ/aroQ-notes.md Soluble cytosolic enzyme (no signal peptide or transmembrane segment; small 147-residue dodecamer). |
| GO:0009423 chorismate biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated IEA from the HAMAP MF_00169 UniRule and UniPathway UPA00053 (chorismate biosynthesis, step 3/7). Reason: AroQ is the only 3-dehydroquinase of M. tuberculosis H37Rv and its role there is biosynthetic (Reactome states it does not take part in catabolism), so it performs step 3 of the pathway to chorismate. The PTHR21272 family review leaves this term UNRESOLVED at family level because SF3 mixes biosynthetic and catabolic members, and asks for per-gene evidence; for this gene the evidence is clear. Supporting Evidence: file:MYCTU/aroQ/aroQ-notes.md returned only P9WPX7 (aroQ, Rv2537c), so AroQ is the only annotated 3-dehydroquinase of M. tuberculosis H37Rv Reactome:R-MTU-964851 Unlike fungi DHQ dehydratases, AroQ doesn't take part in catabolism reactions (Moore et al, 1992). PMID:10360352 Both enzymes function as part of the shikimate pathway |
| GO:0019631 quinate catabolic process | IBA GO_REF:0000033 | REMOVE | Summary: PAINT IBA placing quinate catabolism at the PTHR21272 root node PTN000479790, with A. nidulans QutE as the only seed. Reason: Over-propagation. The PTHR21272 family review assesses this IBD as TOO_DEEP and scopes quinate catabolism to SF5 (Pezizomycotina QutE/qa-2); AroQ is in SF3. In M. tuberculosis AroQ is the sole, biosynthetic dehydroquinase, and Reactome states that it does not take part in catabolism. Its ability to rescue quinate use in an A. nidulans qutE mutant shows catalytic capacity in a heterologous pathway, not participation in quinate catabolism in its own organism. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000479790 SUPPORTS SOURCE BUT NOT TARGET The IBD rests on A. nidulans QutE (P05147) of the fungal quinic acid utilization cluster; placing it at the family root passes the catabolic process to bacterial biosynthetic AroQ enzymes. The family review recommends moving it to the Pezizomycotina node PTN002723599. Supporting Evidence: Reactome:R-MTU-964851 Unlike fungi DHQ dehydratases, AroQ doesn't take part in catabolism reactions (Moore et al, 1992). file:MYCTU/aroQ/aroQ-notes.md This shows catalytic capacity in a heterologous catabolic pathway, not a catabolic role in M. tuberculosis. |
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Download this section (compressed HTML)Q: Should the PAINT quinate catabolic process IBD (PTN000479790) be moved to the Pezizomycotina node PTN002723599 so that bacterial biosynthetic type II enzymes such as M. tuberculosis AroQ no longer inherit it?
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