Related Experiment Video
Updated: Jun 17, 2026

Using Modified Synthetic Oligonucleotides to Assay Nucleic Acid-Metabolizing Enzymes
Published on: July 5, 2024
Structure and mechanism of the lincosamide antibiotic adenylyltransferase LinB
Mariya Morar1, Kirandeep Bhullar1, Donald W Hughes1
1M.G. DeGroote Institute for Infectious Disease Research, Department of Biochemistry and Biomedical Sciences and the Department of Chemistry, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Abstract:
Lincosamides make up an important class of antibiotics used against a wide range of pathogens, including methicillin-resistant Staphylococcus aureus. Predictably, lincosamide-resistant microorganisms have emerged with antibiotic modification as one of their major resistance strategies. Inactivating enzymes LinB/A catalyze adenylylation of the drug; however, little is known about their mechanistic and structural properties. We determined two X-ray structures of LinB: ternary substrate- and binary product-bound complexes. Structural and kinetic characterization of LinB, mutagenesis, solvent isotope effect, and product inhibition studies are consistent with a mechanism involving direct in-line nucleotidyl transfer. The characterization of LinB enabled its classification as a member of a nucleotidyltransferase superfamily, along with nucleotide polymerases and aminoglycoside nucleotidyltransferases, and this relationship offers further support for the LinB mechanism. The LinB structure provides an evolutionary link to ancient nucleotide polymerases and suggests that, like protein kinases and acetyltransferases, these are proto-resistance elements from which drug resistance can evolve.
More Related Videos
12:07Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
Published on: November 22, 2014
08:46Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides
Published on: July 26, 2018
Related Concept Videos
Ligand Binding and Linkage
Allosteric Proteins-ATCase
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Inhibitors of Bacterial Protein Synthesis
Nucleic Acid Structure
DNA Structure
DNA has a double-helix structure. The...
ATP Synthase: Mechanism
Inhibitors of Gram-positive Cell Wall Synthesis