Publication

Article Metrics

Citations


Online attention

Structural characterization of a short-chain dehydrogenase/reductase from multi-drug resistant Acinetobacter baumannii

DOI: 10.1016/j.bbrc.2019.08.056 DOI Help

Authors: Emily M. Cross (Charles Sturt University) , David Aragao (Australian Synchrotron; Diamond Light Source) , Kate M. Smith (Charles Sturt University; Australian Synchrotron) , Karli I. Shaw (Charles Sturt University) , Jeffrey D. Nanson (University of Queensland) , Shane R. Raidal (Charles Sturt University) , Jade K. Forwood (Charles Sturt University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochemical And Biophysical Research Communications

State: Published (Approved)
Published: August 2019

Abstract: Acinetobacter baumannii (A. baumannii) is a clinically relevant, highly drug-resistant pathogen of global concern. An attractive approach to drug design is to specifically target the type II fatty acid synthesis (FASII) pathway which is critical in Gram negative bacteria and is significantly different to the type I fatty acid synthesis (FASI) pathway found in mammals. Enzymes involved in FASII include members of the short-chain dehydrogenase/reductase (SDR) superfamily. SDRs are capable of performing a diverse range of biochemical reactions against a broad spectrum of substrates whilst maintaining conserved structural features and sequence motifs. Here, we use X-ray crystallography to describe the structure of an SDR from the multi-drug resistant bacteria A. baumannii, previously annotated as a putative FASII FabG enzyme. The protein was recombinantly expressed, purified, and crystallized. The protein crystals diffracted to 2.0 Å and the structure revealed a FabG-like fold. Functional assays revealed, however, that the protein was not active against the FabG substrate, acetoacetyl-CoA. This study highlights that database annotations may show the necessary structural hallmarks of such proteins, however, they may not be able to cleave substrates that are typical of FabG enzymes. These results are important for the selection of target enzymes in future drug development.

Journal Keywords: Acinetobacter baumannii; Structure; Enzyme; FabG; SDR; Fatty acid synthesis

Diamond Keywords: Bacteria; Enzymes

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Facility: Australian Synchrotron

Added On: 28/08/2019 12:05

Discipline Tags:

Life Sciences & Biotech Health & Wellbeing Antibiotic Resistance Drug Discovery Infectious Diseases Pathogens Structural biology Chemistry Biochemistry

Technical Tags: