TY - JOUR
T1 - Evidence for Porphyrin-Mediated Electron Transfer in the Radical SAM Enzyme HutW
AU - Brimberry, Marley
AU - Corrigan, Patrick
AU - Silakov, Alexey
AU - Lanzilotta, William N.
N1 - Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society.
PY - 2023/3/21
Y1 - 2023/3/21
N2 - Bacteria that infect the human gut must compete for essential nutrients, including iron, under a variety of different metabolic conditions. Several enteric pathogens, including Vibrio cholerae and Escherichia coli O157:H7, have evolved mechanisms to obtain iron from heme in an anaerobic environment. Our laboratory has demonstrated that a radical S-adenosylmethionine (SAM) methyltransferase is responsible for the opening of the heme porphyrin ring and release of iron under anaerobic conditions. Furthermore, the enzyme in V. cholerae, HutW, has recently been shown to accept electrons from NADPH directly when SAM is utilized to initiate the reaction. However, how NADPH, a hydride donor, catalyzes the single electron reduction of a [4Fe-4S] cluster, and/or subsequent electron/proton transfer reactions, was not addressed. In this work, we provide evidence that the substrate, in this case, heme, facilitates electron transfer from NADPH to the [4Fe-4S] cluster. This study uncovers a new electron transfer pathway adopted by radical SAM enzymes and further expands our understanding of these enzymes in bacterial pathogens.
AB - Bacteria that infect the human gut must compete for essential nutrients, including iron, under a variety of different metabolic conditions. Several enteric pathogens, including Vibrio cholerae and Escherichia coli O157:H7, have evolved mechanisms to obtain iron from heme in an anaerobic environment. Our laboratory has demonstrated that a radical S-adenosylmethionine (SAM) methyltransferase is responsible for the opening of the heme porphyrin ring and release of iron under anaerobic conditions. Furthermore, the enzyme in V. cholerae, HutW, has recently been shown to accept electrons from NADPH directly when SAM is utilized to initiate the reaction. However, how NADPH, a hydride donor, catalyzes the single electron reduction of a [4Fe-4S] cluster, and/or subsequent electron/proton transfer reactions, was not addressed. In this work, we provide evidence that the substrate, in this case, heme, facilitates electron transfer from NADPH to the [4Fe-4S] cluster. This study uncovers a new electron transfer pathway adopted by radical SAM enzymes and further expands our understanding of these enzymes in bacterial pathogens.
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U2 - 10.1021/acs.biochem.2c00474
DO - 10.1021/acs.biochem.2c00474
M3 - Article
C2 - 36877586
AN - SCOPUS:85149731777
SN - 0006-2960
VL - 62
SP - 1191
EP - 1196
JO - Biochemistry
JF - Biochemistry
IS - 6
ER -