MvaB is a hydroxymethylglutaryl-CoA lyase that cleaves (S)-3-hydroxy-3-methylglutaryl-CoA to acetoacetate and acetyl-CoA. This shared terminal reaction can receive HMG-CoA from distal L-leucine catabolism and from other degradative pathways.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003824 catalytic activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic catalytic activity is redundant with the exact lyase term. Reason: Replace the generic catalytic term with the substrate-specific HMG-CoA lyase activity. Proposed replacements: hydroxymethylglutaryl-CoA lyase activity |
| GO:0004419 hydroxymethylglutaryl-CoA lyase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Correct enzyme-specific molecular function. Reason: The UniProt catalytic reaction explicitly cleaves HMG-CoA to acetoacetate and acetyl-CoA. |
| GO:0006552 L-leucine catabolic process | IEA GO_REF:0000118 | ACCEPT | Summary: Plausible terminal role in distal L-leucine catabolism. Reason: The HMG-CoA lyase reaction consumes the product of LiuC. |
| GO:0016833 oxo-acid-lyase activity | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Oxo-acid lyase activity is a broad parent term. Reason: This is a valid parent activity, while the substrate-specific HMG-CoA lyase activity captures the core function. |
| GO:0046872 metal ion binding | ISS PMID:16330546 Crystal structures of two bacterial 3-hydroxy-3-methylglutar... | NEW | Summary: HMG-CoA lyases are DRE-TIM metallolyases with a conserved divalent-cation site. Reason: A divalent cation is a mechanistic requirement of the family, although the preferred ion has not been measured for Q88H25. Supporting Evidence: PMID:16330546 the catalytic center contains a divalent cation-binding site formed by a cluster of invariant residues that cap the core of the barrel file:PSEPK/mvaB/mvaB-uniprot.txt Metal-binding |
| GO:0046951 ketone body biosynthetic process | IEA GO_REF:0000118 | MARK AS OVER ANNOTATED | Summary: The reaction produces acetoacetate, but that product alone does not establish a dedicated ketone-body biosynthetic process. Reason: The GO:0046951 definition describes formation of the ketone bodies acetoacetate, D-3-hydroxybutyrate or acetone, a coordinated ketogenic programme whose physiological output is an exported fuel. MvaB's chemistry produces acetoacetate, so the term is not false at the reaction level, but the pathway context recorded for Q88H25 is degradative rather than ketogenic: UniProt assigns it to metabolic intermediate metabolism, (S)-3-hydroxy-3-methylglutaryl-CoA degradation, acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA, step 1/1 (UniPathway UPA00896/UER00863), and the characterized close ortholog LiuE acts in the leucine/isovalerate catabolic route. P. putida KT2440 has no described ketone-body physiology, and the acetoacetate released here is a catabolic intermediate. The annotation is therefore retained as an over-annotation: a whole-pathway process term attributed to a single enzyme on the strength of its product, with the supported process term GO:0006552 L-leucine catabolic process already carried. |
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Download this section (compressed HTML)Q: How is mvaB expression coordinated with the physically separated ivd-mccB-liuC-mccA cluster during growth on leucine or isovalerate?
Experiment: Measure HMG-CoA cleavage by purified MvaB across Mg2+, Mn2+, and metal-chelated conditions, and compare leucine growth phenotypes of mvaB, PP_3394, and double deletions.
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