3JZ0: LinB complexed with clindamycin and AMPCPP

Citation:
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.
PDB ID: 3JZ0Download
MMDB ID: 77864
PDB Deposition Date: 2009/9/22
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 3JZ0: dimeric; determined by author and by software (PISA)
Molecular Components in 3JZ0
Label Count Molecule
Proteins (2 molecules)
2
Lincosamide Nucleotidyltransferase
Molecule annotation
Chemicals (9 molecules)
1
5
2
2
3
2
* Click molecule labels to explore molecular sequence information.

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