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Title | Cryo-EM Structure of the Mnx Protein Complex Reveals a Tunnel Framework for the Mechanism of Manganese Biomineralization. |
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Journal, issue, pages | J Am Chem Soc, Vol. 146, Issue 33, Page 22950-22958, Year 2024 |
Publish date | Aug 21, 2024 |
Authors | Irina V Novikova / Alexandra V Soldatova / Trevor H Moser / Stephanie M Thibert / Christine A Romano / Mowei Zhou / Bradley M Tebo / James E Evans / Thomas G Spiro / |
PubMed Abstract | The global manganese cycle relies on microbes to oxidize soluble Mn(II) to insoluble Mn(IV) oxides. Some microbes require peroxide or superoxide as oxidants, but others can use O directly, via ...The global manganese cycle relies on microbes to oxidize soluble Mn(II) to insoluble Mn(IV) oxides. Some microbes require peroxide or superoxide as oxidants, but others can use O directly, via multicopper oxidase (MCO) enzymes. One of these, MnxG from strain PL-12, was isolated in tight association with small accessory proteins, MnxE and MnxF. The protein complex, called Mnx, has eluded crystallization efforts, but we now report the 3D structure of a point mutant using cryo-EM single particle analysis, cross-linking mass spectrometry, and AlphaFold Multimer prediction. The β-sheet-rich complex features MnxG enzyme, capped by a heterohexameric ring of alternating MnxE and MnxF subunits, and a tunnel that runs through MnxG and its MnxEF cap. The tunnel dimensions and charges can accommodate the mechanistically inferred binuclear manganese intermediates. Comparison with the Fe(II)-oxidizing MCO, ceruloplasmin, identifies likely coordinating groups for the Mn(II) substrate, at the entrance to the tunnel. Thus, the 3D structure provides a rationale for the established manganese oxidase mechanism, and a platform for further experiments to elucidate mechanistic details of manganese biomineralization. |
External links | J Am Chem Soc / PubMed:39056168 |
Methods | EM (single particle) |
Resolution | 3.37 Å |
Structure data | EMDB-45001, PDB-9bxa: |
Source |
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Keywords | METAL TRANSPORT / Complex / multicopper oxidase / manganese biomineralization |