9WVY
NDP-4-keto-6-deoxyglucose-3-dehydratase KsgR in complex with PMP and AKG
Summary for 9WVY
| Entry DOI | 10.2210/pdb9wvy/pdb |
| Descriptor | Putative NDP-4-keto-6-deoxyglucose-3-dehydratase, 4'-DEOXY-4'-AMINOPYRIDOXAL-5'-PHOSPHATE, 2-OXOGLUTARIC ACID (3 entities in total) |
| Functional Keywords | dehydratase, oxidoreductase |
| Biological source | Streptomyces microaureus |
| Total number of polymer chains | 1 |
| Total formula weight | 43012.72 |
| Authors | |
| Primary citation | Li, Y.,Chen, Y.,Shi, J.,Wu, J.,Wang, Y.,Ren, J.,Li, Y.,Zhou, J.,Gao, Q.,Mei, K.,Guo, Z. Characterization of UDP-Sugar 3-Dehydrase KsgR in the Biosynthesis of a Distinctive Multideoxy Diamino-Sugar Kasugamine of Kasugamycin. J.Am.Chem.Soc., 148:19205-19213, 2026 Cited by PubMed Abstract: Kasugamine (2,4-diamino-2,3,4,6-tetradeoxy-d-mannose, ) is a rare multideoxy diamino-sugar forming the core skeleton of the commercial aminoglycoside antibiotic Kasugamycin (KSG, ), an agricultural fungicide that has been used against rice blast disease for more than 60 years. Despite the reported biosynthetic gene cluster (BGC) for , the enzymatic logic leading to the formation of remained unclear. Here, we report the biosynthetic mechanism of . Five enzymes─KsgQ, KsgB, KsgD, KsgR, and KsgC─can biochemically convert uridine diphosphate--acetyl-d-glucosamine (UDP-GlcNAc, ) to generate the sugar donor , which is incorporated into as confirmed by stable isotope-labeled feeding experiments. KsgB is characterized as the first enzyme catalyzing the deacetylation of uridine diphosphate--acetyl-d-mannosamine (UDP-ManNAc, ), while KsgR represents the first UDP-sugar 3-dehydrase catalyzing the C-3 deoxygenation of the KsgD product () via the cofactors pyridoxal-5'-phosphate (PLP) and l-glutamic acid (l-Glu), and employs a ColD-like catalytic mechanism, as shown by crystallographic analysis, molecular docking, and site-directed mutagenesis. Our findings unravel the biosynthetic mysteries of , highlight the intriguing strategies for biosynthesizing diamino-sugars in nature, and provide some evidence for further completely uncovering the biosynthetic logic of . PubMed: 42076866DOI: 10.1021/jacs.6c03331 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.3 Å) |
Structure validation
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