Asset Details
Do you wish to reserve the book?
Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair
Do you wish to request the book?
Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair
2019
Overview
Itaconate is an immunometabolite with both anti-inflammatory and bactericidal effects. Its coenzyme A (CoA) derivative, itaconyl-CoA, inhibits B12-dependent methylmalonyl-CoA mutase (MCM) by an unknown mechanism. We demonstrate that itaconyl-CoA is a suicide inactivator of human and Mycobacterium tuberculosis MCM, which forms a markedly air-stable biradical adduct with the 5′-deoxyadenosyl moiety of the B12 coenzyme. Termination of the catalytic cycle in this way impairs communication between MCM and its auxiliary repair proteins. Crystallography and spectroscopy of the inhibited enzyme are consistent with a metal-centered cobalt radical ~6 angstroms away from the tertiary carbon-centered radical and suggest a means of controlling radical trajectories during MCM catalysis. Mycobacterial MCM thus joins enzymes in the glyoxylate shunt and the methylcitrate cycle as targets of itaconate in pathogen propionate metabolism.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Cobalt
/ Electron Spin Resonance Spectroscopy
/ Enzymes
/ Humans
/ Methylmalonyl-CoA Mutase - antagonists & inhibitors
/ Methylmalonyl-CoA Mutase - chemistry
/ Methylmalonyl-CoA Mutase - metabolism
/ Mycobacterium tuberculosis - enzymology
/ Mycobacterium tuberculosis - growth & development
/ Mycobacterium tuberculosis - metabolism
/ Protein Subunits - chemistry
/ Protein Subunits - metabolism
/ Repair
/ Suicide
