6jw8

The crystal structure of KanD2 in complex with NADH and 3"-deamino-3"-hydroxykanamycin B

spinqualitylabelsall models 6jw8, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6jw8 is a 2 chain structure with sequence from Streptomyces kanamyceticus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: CK0, NAI Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q6L737_STRKN Publication Abstract from PubMed Kanosamine (3-amino-3-deoxy-d-glucose) is a characteristic sugar unit found in kanamycins, a group of aminoglycoside antibiotics. The kanosamine moiety originates from d-glucose in kanamycin biosynthesis. However, the timing of the replacement of the 3-OH group of the d-glucose-derived biosynthetic intermediate with the amino group is elusive. Comparison of biosynthetic gene clusters for related aminoglycoside antibiotics suggests that the nicotinamide adenine dinucleotide (NAD(+))-dependent dehydrogenase KanD2 and the pyridoxal 5'-phosphate (PLP)-dependent aminotransferase KanS2 are responsible for the introduction of the amino group at the C3 position of kanosamine. In this study, we demonstrated that KanD2 and KanS2 convert kanamycin A, B, and C to the corresponding 3-deamino-3-hydroxykanamycins (3-hks) in the presence of PLP, 2-oxoglutarate, and NADH via a reverse reaction in the pathway. Furthermore, we observed that all of the 3-hks are oxidized by KanD2 with NAD(+), but d-glucose, UDP-d-glucose, d-glucose 6-phosphate, and d-glucose 1-phosphate are not. Crystal structure analysis of KanD2 complexed with 3-hkB and NADH illustrated the selective recognition of pseudotrisaccharides, especially the d-glucose moiety with 2-deoxystreptamine, by a combination of hydrogen bonds and CH-pi interactions. Overall, it was clarified that the kanosamine moiety of kanamycins is constructed after the glucosylation of the pseudodisaccharide biosynthetic intermediates in kanamycin biosynthesis. Biochemical and Structural Analysis of a Dehydrogenase, KanD2, and an Aminotransferase, KanS2, That Are Responsible for the Construction of the Kanosamine Moiety in Kanamycin Biosynthesis.,Kudo F, Kitayama Y, Miyanaga A, Hirayama A, Eguchi T Biochemistry. 2020 Apr 6. doi: 10.1021/acs.biochem.0c00204. PMID:32237736 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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