5u1e

Crystal structure of a methyltransferase involved in the biosynthesis of gentamicin in complex with the kanamycin B

spinqualitylabelsall models 5u1e, resolution 2.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5u1e is a 1 chain structure with sequence from Micromonospora echinospora. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.213Å Ligands: 9CS, SAH Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q2MG72_MICEC Publication Abstract from PubMed Gentamicins are heavily methylated, clinically valuable pseudotrisaccharide antibiotics produced by Micromonospora echinospora. GenN has been characterized as an S-adenosyl-l-methionine-dependent methyltransferase with low sequence similarity to other enzymes. It is responsible for the 3-N-methylation of 3-dehydro-3-amino-gentamicin A2, an essential modification of ring III in the biosynthetic pathway to the gentamicin C complex. Purified recombinant GenN also efficiently catalyzes 3-N-methylation of related aminoglycosides kanamycin B and tobramycin, which both contain an additional hydroxymethyl group at the C5 position in ring III. We have obtained eight cocrystal structures of GenN, at a resolution of 2.2 A or better, including the binary complex of GenN and S-adenosyl-l-homocysteine (SAH) and the ternary complexes of GenN, SAH, and several aminoglycosides. The GenN structure reveals several features not observed in any other N-methyltransferase that fit it for its role in gentamicin biosynthesis. These include a novel N-terminal domain that might be involved in protein:protein interaction with upstream enzymes of the gentamicin X2 biosynthesis and two long loops that are involved in aminoglycoside substrate recognition. In addition, the analysis of structures of GenN in complex with different ligands, supported by the results of active site mutagenesis, has allowed us to propose a catalytic mechanism and has revealed the structural basis for the surprising ability of native GenN to act on these alternative substrates. Structural Basis of the Selectivity of GenN, an Aminoglycoside N-Methyltransferase Involved in Gentamicin Biosynthesis.,Bury PDS, Huang F, Li S, Sun Y, Leadlay PF, Dias MVB ACS Chem Biol. 2017 Oct 9. doi: 10.1021/acschembio.7b00466. PMID:28876898 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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