mtdA

id: P55818
gene_symbol: mtdA
product_type: PROTEIN
taxon:
  id: NCBITaxon:272630
  label: Methylorubrum extorquens AM1
description: 'mtdA encodes a bifunctional NADP-dependent dehydrogenase that catalyzes
  the oxidation of both methylene-H4MPT (EC 1.5.1.-) and methylene-H4F (EC 1.5.1.5)
  to their respective methenyl forms. The enzyme functions in step 2/5 of formaldehyde
  degradation via the H4MPT route, but with a 20-fold preference for H4MPT over H4F
  as substrate (Vmax 600 vs 30 μmol/min/mg). MtdA plays a critical regulatory role
  in controlling the segregation of C1 carbon flux between assimilation and oxidation
  pathways. While mtdB serves as the main methylene-H4MPT dehydrogenase in vivo, mtdA''s
  dual substrate specificity allows it to bridge the H4MPT and tetrahydrofolate metabolic
  pools. The enzyme functions as a homotrimer in the cytoplasm with optimal activity
  at pH 6.0 and 45°C. Multiple crystal structures have been solved (PDB: 1LU9, 1LUA,
  6TGE, 6TLK, 6TM3), including complexes with NADP showing re-face stereospecificity.
  Direct protein sequencing has confirmed the N-terminal sequence.'
existing_annotations:
- term:
    id: GO:0004488
    label: methylenetetrahydrofolate dehydrogenase (NADP+) activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Correct - MtdA catalyzes methylene-H4F dehydrogenation with NADP+ as
      cofactor, though with 20-fold lower efficiency than H4MPT [file:METEA/mtdA/mtdA-uniprot.txt,
      "Can also catalyze the reversible dehydrogenation of methylene-H(4)F with 20-fold
      lower catalytic efficiency...EC=1.5.1.5"].
    action: ACCEPT
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'Correct - MtdA is localized to the cytoplasm where it participates in
      C1 metabolism [file:METEA/mtdA/mtdA-uniprot.txt, "SUBCELLULAR LOCATION: Cytoplasm"].'
    action: ACCEPT
- term:
    id: GO:0006730
    label: one-carbon metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: 'Correct - MtdA is central to C1 metabolism, bridging H4MPT and H4F pathways
      [file:METEA/mtdA/mtdA-uniprot.txt, "One-carbon metabolism; formaldehyde degradation;
      formate from formaldehyde (H(4)MPT route): step 2/5"].'
    action: ACCEPT
- term:
    id: GO:0016491
    label: oxidoreductase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Correct but too general - MtdA is a bifunctional dehydrogenase; more
      specific terms available (GO:0004488 for H4F activity).
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0046294
    label: formaldehyde catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  review:
    summary: 'Correct - MtdA catalyzes step 2/5 in formaldehyde degradation via H4MPT
      route [file:METEA/mtdA/mtdA-uniprot.txt, "formaldehyde degradation; formate
      from formaldehyde (H(4)MPT route): step 2/5"].'
    action: ACCEPT
core_functions:
- description: MtdA is a bifunctional NADP-dependent dehydrogenase that catalyzes
    the oxidation of methylene-H4MPT to methenyl-H4MPT (step 2/5 in formaldehyde degradation)
    and also oxidizes methylene-H4F to methenyl-H4F, albeit with 20-fold lower catalytic
    efficiency (Vmax 600 vs 30 μmol/min/mg). This dual specificity allows MtdA to
    bridge the H4MPT and tetrahydrofolate metabolic pools. The enzyme functions as
    a homotrimer with optimal activity at pH 6.0 and 45°C. While mtdB serves as the
    main methylene-H4MPT dehydrogenase in vivo, MtdA plays a critical regulatory role
    in controlling the segregation of C1 carbon flux between oxidation (via H4MPT)
    and assimilation (via H4F/serine cycle). Crystal structures reveal re-face stereospecificity
    for NADP binding. MtdA represents an evolutionary adaptation linking methylotrophic
    and general C1 metabolism.
  molecular_function:
    id: GO:0004488
    label: methylenetetrahydrofolate dehydrogenase (NADP+) activity
  directly_involved_in:
  - id: GO:0046294
    label: formaldehyde catabolic process
  - id: GO:0006730
    label: one-carbon metabolic process
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:METEA/mtdA/mtdA-uniprot.txt
    supporting_text: Catalyzes the dehydrogenation of methylene-H(4)MPT. Can also
      catalyze the reversible dehydrogenation of methylene-H(4)F with 20-fold lower
      catalytic efficiency...Vmax=600 umol/min/mg enzyme with methylenetetrahydromethanopterin
      as substrate...Vmax=30 umol/min/mg enzyme with methylenetetrahydrofolate as
      substrate...Optimum pH is 6.0...Optimum temperature is 45 degrees Celsius...Homotrimer
  - reference_id: PMID:9765566
    supporting_text: The NADP-dependent methylene tetrahydromethanopterin dehydrogenase
      in Methylobacterium extorquens AM1
references:
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping.
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt.
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods.
  findings: []
status: COMPLETE