8VXB

Structure of ANT(6)-Ib from Campylobacter fetus subsp fetus complexed with hydrated streptomycin

Summary for 8VXB

• Entry DOI: 10.2210/pdb8vxb/pdb
• Descriptor: Streptomycin aminoglycoside adenylyltransferase ant(6)-Ib, [(2~{S},3~{S},4~{S},5~{R},6~{S})-2-[(2~{R},3~{R},4~{R},5~{S})-2-[(1~{R},2~{S},3~{R},4~{R},5~{S},6~{R})-2,4-bis[[azaniumylidene(azanyl)methyl]amino]-3,5,6-tris(oxidanyl)cyclohexyl]oxy-4-[bis(oxidanyl)methyl]-5-methyl-4-oxidanyl-oxolan-3-yl]oxy-6-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-3-yl]-methyl-azanium, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: campylobacter, streptomycin, antibiotic resistance, transferase
• Biological source: Campylobacter fetus subsp. fetus
• Total number of polymer chains: 1
• Total formula weight: 37215.36

Authors

Nalam, P.,Cook, P.,Smith, B. (deposition date: 2024-02-04, release date: 2024-09-18, Last modification date: 2025-01-15)

Primary citation

Nalam, P.,Cook, P.D.,Smith, B.A.
Structural and Biochemical Characterization of Aminoglycoside Nucleotidyltransferase(6)-Ib From Campylobacter fetus subsp. fetus.
Proteins, 93:413-419, 2025

PubMed Abstract: Aminoglycoside antibiotics have played a critical role in the treatment of both Gram-negative and Gram-positive bacterial infections. However, antibiotic resistance has severely compromised the efficacy of aminoglycosides. A leading cause of aminoglycoside resistance is mediated by bacterial enzymes that inactivate these drugs via chemical modification. Aminoglycoside nucleotidyltransferase-6 (ANT(6)) enzymes inactivate streptomycin by transferring an adenyl group from ATP to position 6 on the antibiotic. Despite the clinical significance of this activity, ANT(6) enzymes remain relatively uncharacterized. Here, we report the first high resolution x-ray crystallographic structure of ANT(6)-Ib from Campylobacter fetus subsp. fetus bound with streptomycin. Structural modeling and gel filtration chromatography experiments suggest that the enzyme exists as a dimer in which both subunits contribute to the active site. Moreover, superposition of the ANT(6)-Ib structure with the structurally related enzyme lincosamide nucleotidyltransferase B (LinB) permitted the identification of a putative nucleotide binding site. These data also suggest that residues D44 and D46 coordinate essential divalent metal ions and D102 functions as the catalytic base.

PubMed: 39246239
DOI: 10.1002/prot.26745

Experimental method

X-RAY DIFFRACTION (1.85 Å)