5IG8: Crystal Structure Of Macrocyclase Mdnb From Microcystis Aeruginosa Mrc

Macrocyclization is a common feature of natural product biosynthetic pathways including the diverse family of ribosomal peptides. Microviridins are architecturally complex cyanobacterial ribosomal peptides that target proteases with potent reversible inhibition. The product structure is constructed via three macrocyclizations catalyzed sequentially by two members of the ATP-grasp family, a unique strategy for ribosomal peptide macrocyclization. Here we describe in detail the structural basis for the enzyme-catalyzed macrocyclizations in the microviridin J pathway of Microcystis aeruginosa. The macrocyclases MdnC and MdnB interact with a conserved alpha-helix of the precursor peptide using a novel precursor-peptide recognition mechanism. The results provide insight into the unique protein-protein interactions that are key to the chemistry, suggest an origin for the natural combinatorial synthesis of microviridin peptides, and provide a framework for future engineering efforts to generate designed compounds.
PDB ID: 5IG8Download
MMDB ID: 143282
PDB Deposition Date: 2016/2/27
Updated in MMDB: 2016/10
Experimental Method:
x-ray diffraction
Resolution: 2.28  Å
Source Organism:
Similar Structures:
Biological Unit for 5IG8: dimeric; determined by author and by software (PISA)
Molecular Components in 5IG8
Label Count Molecule
Proteins (2 molecules)
ATP Grasp Ligase
Molecule annotation
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Citing MMDB