9aue

Crystal structure of the holo form of GenB2 in complex with PMP

spinqualitylabelsall models 9aue, resolution 1.46Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9aue 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 1.46Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q70KE6_MICEC Publication Abstract from PubMed Aminoglycosides are essential antibiotics used to treat severe infections caused mainly by Gram-negative bacteria. Gentamicin is an aminoglycoside and, despite its toxicity, is clinically used to treat several pulmonary and urinary infections. The commercial form of gentamicin is a mixture of five compounds with minor differences in the methylation of one of their aminosugars. In the case of two compounds, gentamicin C2 and C2a, the only difference is the stereochemistry of the methyl group attached to C-6'. GenB2 is the enzyme responsible for this epimerization and is one of the four PLP-dependent enzymes encoded by the gentamicin biosynthetic gene cluster. Herein, we have determined the structure of GenB2 in its holo form in complex with PMP and also in the ternary complex with gentamicin X2 and G418, two substrate analogues. Based on the structural analysis, we were able to identify the structural basis for the catalytic mechanism of this enzyme, which was also studied by site-directed mutagenesis. Unprecedently, GenB2 is a PLP-dependent enzyme from fold I, which is able to catalyze an epimerization but with a mechanism distinct from that of fold III PLP-dependent epimerases using a cysteine residue near the N-terminus. The substitution of this cysteine residue for serine or alanine completely abolished the epimerase function of the enzyme, confirming its involvement. This study not only contributes to the understanding of the enzymology of gentamicin biosynthesis but also provides valuable details for exploring the enzymatic production of new aminoglycoside derivatives. Structural and Functional Basis of GenB2 Isomerase Activity from Gentamicin Biosynthesis.,Oliveira GS, Dos S Bury P, Huang F, Li Y, Araujo NC, Zhou J, Sun Y, Leeper FJ, Leadlay PF, Dias MVB ACS Chem Biol. 2024 Aug 29. doi: 10.1021/acschembio.4c00334. PMID:39207862 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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