6F32
Crystal structure of a dual function amine oxidase/cyclase in complex with substrate analogues
Summary for 6F32
| Entry DOI | 10.2210/pdb6f32/pdb |
| Descriptor | Amine oxidase LkcE, FLAVIN-ADENINE DINUCLEOTIDE, ACETATE ION, ... (8 entities in total) |
| Functional Keywords | amine oxydase, cyclase, post-pks enzyme, tayloring enzyme, flavoprotein |
| Biological source | Streptomyces rochei (Streptomyces parvullus) |
| Total number of polymer chains | 2 |
| Total formula weight | 101723.41 |
| Authors | Dorival, J.,Risser, F.,Jacob, C.,Collin, S.,Drager, G.,Kirschning, A.,Paris, C.,Chagot, B.,Gruez, A.,Weissman, K.J. (deposition date: 2017-11-27, release date: 2018-09-19, Last modification date: 2024-05-08) |
| Primary citation | Dorival, J.,Risser, F.,Jacob, C.,Collin, S.,Drager, G.,Paris, C.,Chagot, B.,Kirschning, A.,Gruez, A.,Weissman, K.J. Insights into a dual function amide oxidase/macrocyclase from lankacidin biosynthesis. Nat Commun, 9:3998-3998, 2018 Cited by PubMed Abstract: Acquisition of new catalytic activity is a relatively rare evolutionary event. A striking example appears in the pathway to the antibiotic lankacidin, as a monoamine oxidase (MAO) family member, LkcE, catalyzes both an unusual amide oxidation, and a subsequent intramolecular Mannich reaction to form the polyketide macrocycle. We report evidence here for the molecular basis for this dual activity. The reaction sequence involves several essential active site residues and a conformational change likely comprising an interdomain hinge movement. These features, which have not previously been described in the MAO family, both depend on a unique dimerization mode relative to all structurally characterized members. Taken together, these data add weight to the idea that designing new multifunctional enzymes may require changes in both architecture and catalytic machinery. Encouragingly, however, our data also show LkcE to bind alternative substrates, supporting its potential utility as a general cyclization catalyst in synthetic biology. PubMed: 30266997DOI: 10.1038/s41467-018-06323-w PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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