6BBZ

Room temperature neutron/X-ray structure of sisomicin bound AAC-VIa

Summary for 6BBZ

• Entry DOI: 10.2210/pdb6bbz/pdb
• Related: 6BBR
• Descriptor: AAC 3-VI protein, (1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2S,3R)-3-amino-6-(aminomethyl)-3,4-dihydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl 3-deoxy-4-C-methyl-3-(methylamino)-beta-L-arabinopyranoside, MAGNESIUM ION, ... (4 entities in total)
• Functional Keywords: acetyltransferase, transferase-antibiotic complex, transferase/antibiotic
• Biological source: Enterobacter cloacae
• Total number of polymer chains: 1
• Total formula weight: 32816.29

Authors

Cuneo, M.J.,Kumar, P. (deposition date: 2017-10-20, release date: 2018-02-28, Last modification date: 2023-10-04)

Primary citation

Kumar, P.,Serpersu, E.H.,Cuneo, M.J.
A low-barrier hydrogen bond mediates antibiotic resistance in a noncanonical catalytic triad.
Sci Adv, 4:eaas8667-eaas8667, 2018

PubMed Abstract: One group of enzymes that confer resistance to aminoglycoside antibiotics through covalent modification belongs to the GCN5-related -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.

PubMed: 29632894
DOI: 10.1126/sciadv.aas8667

Experimental method

NEUTRON DIFFRACTION (2.2 Å)
X-RAY DIFFRACTION (1.9 Å)