Mar 5, 2014

Structural recognition of spectinomycin by resistance enzyme ANT(9) from Enterococcus faecalis

BioRxiv : the Preprint Server for Biology
Jennifer Gardy, Caroline Colijn

Abstract

Spectinomycin is a ribosome-binding antibiotic that blocks the translocation step of translation. A prevalent resistance mechanism is the modification of the drug by aminoglycoside nucleotidyl transferase (ANT) enzymes of the spectinomycin-specific ANT(9) family or by the dual-specificity ANT(3")(9) family that also acts on streptomycin. We previously reported the structural mechanism of streptomycin modification by the ANT(3")(9) AadA from Salmonella enterica. ANT(9) from Enterococcus faecalis adenylates the 9-hydroxyl of spectinomycin. We here present the first structures of spectinomycin bound to an ANT enzyme. Structures were solved for ANT(9) in apo form, in complex with ATP, spectinomycin and magnesium or in complex with only spectinomycin. ANT(9) shows similar overall structure as AadA with an N-terminal nucleotidyltransferase domain and a C-terminal α-helical domain. Spectinomycin binds close to the entrance of the interdomain cleft, while ATP is buried at the bottom. Upon drug binding, the C-terminal domain rotates by 14 degrees to close the cleft, allowing contacts of both domains with the drug. Comparison with AadA shows that spectinomycin specificity is explained by a straight α5 helix and a shorter α5-α6 loop that ...Continue Reading

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Mentioned in this Paper

Patterns
Classification
Genome
Trees (plant)
SNAP25
Phylogenetic Analysis
Disease Transmission
Structure
Signal Transmission via Phosphorylation Event
Disease Management

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