Unknown

Dataset Information

0

Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria.

ABSTRACT: FadE, an acyl-CoA dehydrogenase, introduces unsaturation to carbon chains in lipid metabolism pathways. Here, we report that FadE5 from Mycobacterium tuberculosis (MtbFadE5) and Mycobacterium smegmatis (MsFadE5) 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 MsFadE5 and MtbFadE5, 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 ?-? 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.

SUBMITTER: Chen X 

PROVIDER: S-EPMC7368279 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Structural basis for the broad substrate specificity of two acyl-CoA dehydrogenases FadE5 from mycobacteria.

Chen Xiaobo X   Chen Jiayue J   Yan Bing B   Zhang Wei W   Guddat Luke W LW   Liu Xiang X   Rao Zihe Z  

Proceedings of the National Academy of Sciences of the United States of America 20200629 28

FadE, an acyl-CoA dehydrogenase, introduces unsaturation to carbon chains in lipid metabolism pathways. Here, we report that FadE5 from <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>FadE5) and <i>Mycobacterium smegmatis</i> (<i>Ms</i>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 <i>Ms</i>FadE5 and <i>Mtb</i>FadE5, in the presence and absence of substrates, have been  ...[more]

Similar Datasets

Unknown Structural Basis for Substrate Specificity in Adenosylcobalamin-dependent Isobutyryl-CoA Mutase and Related Acyl-CoA Mutases.
| S-EPMC4646380 | biostudies-literature
Unknown Structural basis for substrate specificity of methylsuccinyl-CoA dehydrogenase, an unusual member of the acyl-CoA dehydrogenase family.
| S-EPMC5798300 | biostudies-literature
Unknown Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase.
| S-EPMC2431035 | biostudies-literature
Unknown Structural basis for the activity and substrate specificity of fluoroacetyl-CoA thioesterase FlK.
| S-EPMC2903362 | biostudies-literature
Unknown Structural basis for the broad substrate specificity of the human tyrosylprotein sulfotransferase-1.
| S-EPMC5562738 | biostudies-literature
Unknown Acyl-CoA dehydrogenases: Dynamic history of protein family evolution.
| S-EPMC4136416 | biostudies-literature
Unknown Allosteric modulation of the substrate specificity of acyl-CoA wax alcohol acyltransferase 2.
| S-EPMC5392747 | biostudies-literature
Unknown Crystal structure of the Mycobacterium fortuitum class A beta-lactamase: structural basis for broad substrate specificity.
| S-EPMC1489783 | biostudies-literature
Unknown Identification and characterization of new long chain acyl-CoA dehydrogenases.
| S-EPMC3073726 | biostudies-literature
Unknown Structural basis for substrate specificity of mammalian neuraminidases.
| S-EPMC4164519 | biostudies-literature