PDBsum entry 6bc5

Transferase

PDB id: 6bc5

Contents

Protein chain

268 a.a.

Ligands

COA

Waters ×129

References listed in PDB file

Key reference

• Title: A low-Barrier hydrogen bond mediates antibiotic resistance in a noncanonical catalytic triad.
• Authors: P.Kumar, E.H.Serpersu, M.J.Cuneo.
• Ref.: Sci Adv, 2018, 4, eaas8667.
• PubMed id: 29632894

Abstract

One group of enzymes that confer resistance to aminoglycoside antibiotics through covalent modification belongs to the GCN5-related N-acetyltransferase (GNAT) superfamily. We show how a unique GNAT subfamily member uses a previously unidentified noncanonical catalytic triad, consisting of a glutamic acid, a histidine, and the antibiotic substrate itself, which acts as a nucleophile and attacks the acetyl donor molecule. Neutron diffraction studies allow for unambiguous identification of a low-barrier hydrogen bond, predicted in canonical catalytic triads to increase basicity of the histidine. This work highlights the role of this unique catalytic triad in mediating antibiotic resistance while providing new insights into the design of the next generation of aminoglycosides.