MoaC is the cyclic pyranopterin monophosphate (cPMP) synthase of Escherichia coli, the second enzyme of molybdenum cofactor (Moco) biosynthesis. It receives (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate (3',8-cH2GTP), the product of the radical SAM GTP 3',8-cyclase MoaA, and catalyses the complex rearrangement that builds the pyranopterin ring and cyclic phosphate of cPMP (precursor Z), releasing diphosphate. cPMP is then converted to molybdopterin by the MoaD-MoaE molybdopterin synthase. MoaC is a small cytoplasmic protein with a ferredoxin-like fold that assembles as a homohexamer (trimer of dimers); its active site lies at the interface between two monomers, and residues such as Asp128, Lys51, His77 and Glu112 are required for activity. It is encoded in the anaerobically induced moaABCDE operon and is the bacterial counterpart of the human MOCS1B domain.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:15690043 Interaction network containing conserved and essential prote... | REMOVE | Summary: Co-purification of MoaC with ribosomal protein L1 (rplA, P0A7L0) in a large-scale affinity-purification/mass-spectrometry screen. Reason: Bare protein binding is uninformative under the protein-binding policy, and this high-throughput co-purification with an abundant ribosomal protein identifies no function of MoaC. Removal does not assert that the interaction is false; there is no more informative molecular function that this evidence supports. Supporting Evidence: PMID:15690043 A total of 857 proteins, including 198 of the most highly conserved, soluble non-ribosomal proteins essential in at least one bacterial species, were tagged successfully, whereas 648 could be purified to homogeneity and their interacting protein partners identified by mass spectrometry. |
| GO:0006777 Mo-molybdopterin cofactor biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: MoaC catalyses the second step of Moco biosynthesis, forming cPMP from 3',8-cH2GTP. Reason: MoaC performs a catalytic step of the process (pyranopterin ring formation), so it passes the participation test. Consistent with the IMP and IDA rows and with genes/ECOLI/moaA. Supporting Evidence: PMID:25941396 During Moco biosynthesis, the characteristic pyranopterin ring is constructed by a complex rearrangement of guanosine 5'-triphosphate (GTP) into cyclic pyranopterin (cPMP) through the action of two enzymes, MoaA and MoaC |
| GO:0006777 Mo-molybdopterin cofactor biosynthetic process | IMP PMID:25941396 Mechanism of pyranopterin ring formation in molybdenum cofac... | ACCEPT | Summary: Structure-guided mutagenesis of E. coli MoaC active-site residues abolishes cPMP formation (for example D128A, K51A, H77A and E112A). Reason: Loss-of-function mutants of MoaC abolish the cPMP-forming step, consistent with its established biochemical role. Abstract-only cache, but the UniProt mutagenesis features cite this paper and the claim agrees with the biochemistry; deferring to the curator. Supporting Evidence: file:ECOLI/moaC/moaC-uniprot.txt D->A: Complete loss of activity. PMID:25941396 Furthermore, our structure-guided studies suggest that MoaC catalysis involves the dynamic motions of enzyme active-site loops as a way to control the timing of interaction between the reaction intermediates and catalytically essential amino acid residues. |
| GO:0032991 protein-containing complex | IDA PMID:10903949 Insights into molybdenum cofactor deficiency provided by the... | KEEP AS NON CORE | Summary: The crystal structure shows that E. coli MoaC is a tightly packed homohexamer with the active site at a dimer interface. Reason: The homohexamer is real and structurally required for the active site, but no specific GO complex term exists for a MoaC homo-oligomer, so the generic term is as precise as the evidence allows. It records quaternary structure rather than the core catalytic function. Supporting Evidence: PMID:10903949 The enzyme is organized into a tightly packed hexamer with 32 symmetry. |
| GO:0042802 identical protein binding | IDA PMID:10903949 Insights into molybdenum cofactor deficiency provided by the... | KEEP AS NON CORE | Summary: Self-association of MoaC into a hexamer, with the active site at the interface of two monomers. Reason: Homo-oligomerization is shown structurally and is needed to build the inter-subunit active site, but it is a structural property supporting catalysis, not the core activity. Supporting Evidence: PMID:10903949 Analysis of structural and biochemical data strongly suggests that the active site is located at the interface of two monomers in a pocket that contains several strictly conserved residues. file:ECOLI/moaC/moaC-uniprot.txt SUBUNIT: Homohexamer; trimer of dimers. |
| GO:0061799 cyclic pyranopterin monophosphate synthase activity | IDA PMID:25941396 Mechanism of pyranopterin ring formation in molybdenum cofac... | ACCEPT | Summary: Purified E. coli MoaC converts 3',8-cH2GTP, the MoaA product, into cPMP; the substrate was captured in the MoaC active site. Reason: This is the defining reaction of MoaC (EC 4.6.1.17, RHEA:49580), with kinetic parameters measured in this paper. Core function. Supporting Evidence: PMID:25941396 These observations provided strong evidence that the physiological function of MoaA is the conversion of GTP to 3',8-cH2GTP (GTP 3',8-cyclase), and that of MoaC is to catalyze the rearrangement of 3',8-cH2GTP into cPMP (cPMP synthase). file:ECOLI/moaC/moaC-uniprot.txt KM=0.21 uM for (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate |
| GO:0061799 cyclic pyranopterin monophosphate synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: HAMAP/Rhea mapping to the cPMP synthase reaction. Reason: Consistent with the IDA row and the experimentally supported UniProt function. Supporting Evidence: file:ECOLI/moaC/moaC-uniprot.txt FUNCTION: Catalyzes the conversion of (8S)-3',8-cyclo-7,8- dihydroguanosine 5'-triphosphate to cyclic pyranopterin monophosphate (cPMP). |
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Download this section (compressed HTML)Q: Is the labile 3',8-cH2GTP intermediate channelled from MoaA to MoaC in E. coli through a transient MoaA-MoaC complex, or does it diffuse freely between the enzymes?
Experiment: Compare cPMP yields from coupled versus sequential MoaA/MoaC reactions under anaerobic conditions and test for a MoaA-MoaC complex by crosslinking or native mass spectrometry.
Hypothesis: MoaA and MoaC interact transiently to protect 3',8-cH2GTP.
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