mvaB

UniProt ID: Q88H25
Organism: Pseudomonas putida KT2440
Review Status: DRAFT
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Gene Description

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.

Existing Annotations Review

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.
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.

Core Functions

Cleaves HMG-CoA to acetoacetate and acetyl-CoA at the shared terminal position of distal L-leucine catabolism.

Supporting Evidence:
  • file:PSEPK/mvaB/mvaB-uniprot.txt
    RecName: Full=hydroxymethylglutaryl-CoA lyase
  • file:PSEPK/mvaB/mvaB-deep-research-openscientist.md
    mvaB (PP_3540, Q88H25) of *Pseudomonas putida* KT2440 is **3-hydroxy-3-methylglutaryl-CoA lyase (EC 4.1.3.4)**
  • PMID:19459965
    cleavage of HMG-CoA to acetyl-CoA and acetoacetate.

References

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Suggested Questions for Experts

Q: How is mvaB expression coordinated with the physically separated ivd-mccB-liuC-mccA cluster during growth on leucine or isovalerate?

Suggested Experiments

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.

Deep Research

OpenScientist

(mvaB-deep-research-openscientist.md)

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πŸ“š Additional Documentation

Notes

(mvaB-notes.md)

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