Falcon deep research on pqqE (Edison Scientific Literature, P71517, M. extorquens AM1)
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PqqE is a SPASM-subclass radical SAM enzyme that catalyzes the first committed step of PQQ biosynthesis - installing a C-C cross-link between a conserved glutamate and tyrosine on the ribosomal precursor peptide PqqA, in a PqqD-dependent reaction.
"a **radical S-adenosyl-L-methionine (radical SAM)** enzyme (SPASM subclass) that catalyzes the **first committed chemical step** in pyrroloquinoline quinone (**PQQ**) biosynthesis: **installation of a C–C bond (crosslink) between the side chains of a conserved glutamate and tyrosine on the ribosomally produced precursor peptide PqqA**, in a reaction that requires the peptide chaperone **PqqD**"
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The cross-linking proceeds by 5'-deoxyadenosyl-radical abstraction of a beta-hydrogen from the PqqA glutamate, generating a peptide radical that couples regioselectively to the ortho position of the tyrosine ring to form the PQQ core scaffold (supported by deuterium-labeling kinetic isotope effects).
"The resulting radical **couples regioselectively to the ortho position of a tyrosine ring**, forming the crosslink that constitutes the PQQ core scaffold."
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PqqE binds the canonical radical SAM [4Fe-4S] cluster plus two auxiliary Fe-S clusters (AuxI, AuxII) in its C-terminal SPASM domain; the crystal structure assigns AuxII as a [4Fe-4S] coordinated by three cysteines and Asp319, with AuxI appearing as a [2Fe-2S].
"PqqE contains the canonical radical SAM cluster and **two auxiliary Fe–S clusters (AuxI and AuxII)** in its C-terminal SPASM domain."
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PqqE/PqqD generate a cross-linked PqqA intermediate (PqqA*), an early di-amino-acid precursor that is subsequently excised by the two-component PqqF/PqqG protease and processed by downstream enzymes toward mature PQQ.
"PqqE/PqqD make the crosslink and PqqF/PqqG initiate cleavage"
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PqqE acts in the cytosol on the ribosomal PqqA peptide; the mature PQQ cofactor accumulates in the periplasm where it serves periplasmic methanol/alcohol dehydrogenases central to methylotrophy in M. extorquens AM1.
"PqqE likely acts in the cytosol on PqqA prior to downstream processing and subsequent periplasmic accumulation/use of PQQ"