Structural Basis for Substrate Specificity in Adenosylcobalamin-dependent Isobutyryl-CoA Mutase and Related Acyl-CoA Mutases.

The Journal of Biological Chemistry
Marco JostCatherine L Drennan

Abstract

Acyl-CoA mutases are a growing class of adenosylcobalamin-dependent radical enzymes that perform challenging carbon skeleton rearrangements in primary and secondary metabolism. Members of this class of enzymes must precisely control substrate positioning to prevent oxidative interception of radical intermediates during catalysis. Our understanding of substrate specificity and catalysis in acyl-CoA mutases, however, is incomplete. Here, we present crystal structures of IcmF, a natural fusion protein variant of isobutyryl-CoA mutase, in complex with the adenosylcobalamin cofactor and four different acyl-CoA substrates. These structures demonstrate how the active site is designed to accommodate the aliphatic acyl chains of each substrate. The structures suggest that a conformational change of the 5'-deoxyadenosyl group from C2'-endo to C3'-endo could contribute to initiation of catalysis. Furthermore, detailed bioinformatic analyses guided by our structural findings identify critical determinants of acyl-CoA mutase substrate specificity and predict new acyl-CoA mutase-catalyzed reactions. These results expand our understanding of the substrate specificity and the catalytic scope of acyl-CoA mutases and could benefit engineering ef...Continue Reading

References

Oct 3, 1998·Acta Crystallographica. Section D, Biological Crystallography·A T BrüngerG L Warren
Jul 2, 1999·Applied and Environmental Microbiology·C M So, L Y Young
Feb 7, 2003·Applied and Environmental Microbiology·Olaf KniemeyerFriedrich Widdel
May 2, 2003·Journal of the American Chemical Society·Monica D Vlasie, Ruma Banerjee
Mar 23, 2004·Nucleic Acids Research·Robert C Edgar
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jun 9, 2005·Chemical Reviews·Kenneth L Brown
Jun 23, 2005·Journal of the American Chemical Society·Kasper P Jensen, Ulf Ryde
Mar 23, 2006·Acta Crystallographica. Section D, Biological Crystallography·Jay Painter, Ethan A Merritt
Oct 13, 2006·BMC Bioinformatics·François ChevenetRichard Christen
May 23, 2007·Proceedings of the National Academy of Sciences of the United States of America·Pankaz K SharmaArieh Warshel
Jun 6, 2007·Proceedings of the National Academy of Sciences of the United States of America·Tobias J ErbBirgit E Alber
Nov 17, 2007·Nature Protocols·Axel T Brunger
Apr 22, 2008·Nucleic Acids Research·A DereeperO Gascuel
Sep 23, 2009·Acta Crystallographica. Section D, Biological Crystallography·Nigel W MoriartyPaul D Adams
Oct 30, 2009·The Journal of Biological Chemistry·Valentin CracanRuma Banerjee
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Mar 5, 2011·Chemical Reviews·Jessica L Vey, Catherine L Drennan
Dec 15, 2011·The Journal of Biological Chemistry·Valentin Cracan, Ruma Banerjee
Jan 11, 2012·Journal of the American Chemical Society·Denis BucherDavid M Smith
Mar 27, 2012·Journal of Bacteriology·Christa Ebenau-JehleGeorg Fuchs

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Citations

Jan 29, 2017·The Journal of Biological Chemistry·Zhu LiRuma Banerjee
Sep 9, 2017·The Journal of Biological Chemistry·Gregory C CampanelloRuma Banerjee
Dec 15, 2020·Nucleic Acids Research·Zhesi ZhuY George Zheng
Apr 3, 2021·Accounts of Chemical Research·Ruma BanerjeeShubhadra Pillay
Jul 25, 2020·Protein and Peptide Letters·Eser ÜnsaldıGülay Özcengiz

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