Structural Basis for the Broad Substrate Specificity of Two Acyl-CoA Dehydrogenases FadE5 from Mycobacteria

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2020 Jul 1

PMID 32601219

Citations 8

Authors

Xiaobo Chen

Jiayue Chen

Bing Yan

Wei Zhang

Luke W Guddat

Xiang Liu

Zihe Rao

Affiliations

Soon will be listed here.

Abstract

FadE, an acyl-CoA dehydrogenase, introduces unsaturation to carbon chains in lipid metabolism pathways. Here, we report that FadE5 from (FadE5) and (FadE5) play roles in drug resistance and exhibit broad specificity for linear acyl-CoA substrates but have a preference for those with long carbon chains. Here, the structures of FadE5 and FadE5, in the presence and absence of substrates, have been determined. These reveal the molecular basis for the broad substrate specificity of these enzymes. FadE5 interacts with the CoA region of the substrate through a large number of hydrogen bonds and an unusual π-π stacking interaction, allowing these enzymes to accept both short- and long-chain substrates. Residues in the substrate binding cavity reorient their side chains to accommodate substrates of various lengths. Longer carbon-chain substrates make more numerous hydrophobic interactions with the enzyme compared with the shorter-chain substrates, resulting in a preference for this type of substrate.

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