6PZN

Putative SDR from Acinetobacter baumannii Crystal Form 2

Replaces:  6OV5

Summary for 6PZN

• Entry DOI: 10.2210/pdb6pzn/pdb
• Descriptor: 3-ketoacyl-ACP reductase (2 entities in total)
• Functional Keywords: short-chain dehydrogenase/reductase, sdr, rossmann fold, apo, oxidoreductase, fabg
• Biological source: Acinetobacter baumannii
• Total number of polymer chains: 4
• Total formula weight: 113912.91

Authors

Cross, E.M.,Aragao, D.,Forwood, J.K. (deposition date: 2019-08-01, release date: 2019-08-14, Last modification date: 2023-10-25)

Primary citation

Cross, E.M.,Aragao, D.,Smith, K.M.,Shaw, K.I.,Nanson, J.D.,Raidal, S.R.,Forwood, J.K.
Structural characterization of a short-chain dehydrogenase/reductase from multi-drug resistant Acinetobacter baumannii.
Biochem.Biophys.Res.Commun., 518:465-471, 2019

PubMed 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.

PubMed: 31443964
DOI: 10.1016/j.bbrc.2019.08.056

Experimental method

X-RAY DIFFRACTION (2 Å)