10ZG

Novobiocin Glycosyltransferase (Ngt-1)

Summary for 10ZG

• Entry DOI: 10.2210/pdb10zg/pdb
• Descriptor: Glycosyl transferase, URIDINE-5'-DIPHOSPHATE, NOVOBIOCIN, ... (4 entities in total)
• Functional Keywords: inactivating enzyme, transferase
• Biological source: Bacillus thuringiensis
• Total number of polymer chains: 1
• Total formula weight: 47590.64

Authors

Abbas, A.,Wright, G.D. (deposition date: 2026-02-12, release date: 2026-05-06)

Primary citation

Abbas, A.,Sychantha, D.,Koteva, K.,Chiao, M.,Sokaribo, A.,Hackenberger, D.,Andres, S.,Wright, G.D.
Ngt-1: a glycosyltransferase that confers resistance to three distinct antibiotic classes.
J.Biol.Chem., :111479-111479, 2026

PubMed Abstract: Environmental microbes are a rich source of antibiotic resistance genes with the potential to be mobilized and captured by pathogens under selective pressure. This largely unexplored resistome offers an opportunity to identify novel resistance mechanisms that may eventually emerge in clinical settings, supporting efforts to maintain current antibiotic efficacy. From a screen of environmental bacterial isolates, we identified Bacillus thuringiensis WAC10774B, which confers resistance to the aminocoumarin antibiotic novobiocin through enzymatic inactivation. Analysis of the inactive antibiotic revealed that WAC10774B modifies novobiocin via glycosylation, a unique transformation not reported since the antibiotic's discovery 70 years ago. Using activity-guided protein purification, we identified the novobiocin glycosyltransferase, Ngt-1, and its encoding gene. Surprisingly, ngt-1 confers resistance to three structurally distinct antibiotic classes: novobiocin (aminocoumarin), fidaxomicin (tiacumicin), and salinomycin (polyether). To further explore Ngt-1's functional breadth, we performed steady-state kinetic and protein-structure studies, revealing Ngt-1 as a novel, broad-spectrum glycosyltransferase capable of inactivating antibiotics. These findings highlight the importance of exploring the environmental resistome to identify new resistance enzymes and to inform strategies to combat antimicrobial resistance.

PubMed: 42031167
DOI: 10.1016/j.jbc.2026.111479

Experimental method

X-RAY DIFFRACTION (2 Å)