PDBsum entry 6bbz

Transferase/antibiotic

PDB id: 6bbz

Contents

Protein chain

267 a.a.

Ligands

SIS

Metals

_MG

Waters ×340

PDB id:

6bbz

Name:

Transferase/antibiotic

Title:

Room temperature neutron/x-ray structure of sisomicin bound aac-via

Structure:

Aac 3-vi protein. Chain: a. Synonym: aac-via. Engineered: yes

Source:

Enterobacter cloacae. Organism_taxid: 550. Gene: aac 3-vi. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.90Å R-factor: 0.152 R-free: 0.181

Authors:

M.J.Cuneo,P.Kumar

Key ref:

P.Kumar et al. (2018). A low-barrier hydrogen bond mediates antibiotic resistance in a noncanonical catalytic triad. Sci Adv, 4, eaas8667. PubMed id: 29632894

Date:

20-Oct-17 Release date: 28-Feb-18

Protein chain

Q47030  (Q47030_ENTCL) -  Aminoglycoside N(3)-acetyltransferase from Enterobacter cloacae

Seq: 299 a.a.

Struc: 267 a.a.

Enzyme reactions

• Enzyme class: E.C.2.3.1.81 - aminoglycoside N(3)-acetyltransferase.
• Reaction: a 2-deoxystreptamine antibiotic + acetyl-CoA = an N₃-acetyl-2- deoxystreptamine antibiotic + CoA + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Sci Adv 4:eaas8667 (2018)

PubMed id: 29632894

A low-barrier hydrogen bond mediates antibiotic resistance in a noncanonical catalytic triad.

P.Kumar, E.H.Serpersu, M.J.Cuneo.

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.