9GNC
KvPepIY122A mutant in complex with F420, F420-dependent oxidoreductase
Summary for 9GNC
| Entry DOI | 10.2210/pdb9gnc/pdb |
| Descriptor | Putative F420-dependent oxidoreductase, COENZYME F420 (3 entities in total) |
| Functional Keywords | kvpepiy122a mutant in complex with f420, f420-dependent oxidoreductase, biosynthetic protein |
| Biological source | Streptomyces |
| Total number of polymer chains | 2 |
| Total formula weight | 66166.05 |
| Authors | |
| Primary citation | Mo, J.,Sikandar, A.,Zhao, H.,Bashiri, G.,Huo, L.,Empting, M.,Muller, R.,Fu, C. Tandem ketone reduction in pepstatin biosynthesis reveals an F 420 H 2 -dependent statine pathway. Nat Commun, 16:4531-4531, 2025 Cited by PubMed Abstract: Pepstatins are potent inhibitors of aspartic proteases, featuring two statine residues crucial for target binding. However, the biosynthesis of pepstatins, especially their statine substructure, remains elusive. Here, we discover and characterize an unconventional gene cluster responsible for pepstatin biosynthesis, comprising discrete nonribosomal peptide synthetase and polyketide synthase genes, highlighting its trans-acting and iterative nature. Central to this pathway is PepI, an FH-dependent oxidoreductase. The biochemical characterization of PepI reveals its role in the tandem reduction of β-keto pepstatin intermediates. PepI first catalyzes the formation of the central statine, then produces the C-terminal statine moiety. The post-assembly-line formation of statine by PepI contrasts with the previously hypothesized biosynthesis involving polyketide synthase ketoreductase domains. Structural studies, site-directed mutagenesis, and deuterium-labeled enzyme assays probe the mechanism of FH-dependent oxidoreductases and identify critical residues. Our findings uncover a unique statine biosynthetic pathway employing the only known iterative FH-dependent oxidoreductase to date. PubMed: 40374670DOI: 10.1038/s41467-025-59785-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.65 Å) |
Structure validation
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