5CJU

Isobutyryl-CoA mutase fused with bound adenosylcobalamin, GDP, Mg (holo-IcmF/GDP), and substrate n-butyryl-coenzyme A

5CJU の概要

• エントリーDOI: 10.2210/pdb5cju/pdb
• 関連するPDBエントリー: 4XC6 4XC7 4XC8 5CJT 5CJV 5CJW
• 分子名称: Isobutyryl-CoA mutase fused, COBALAMIN, 5'-DEOXYADENOSINE, ... (6 entities in total)
• 機能のキーワード: radical enzyme, complex, isomerase, g-protein chaperone
• 由来する生物種: Ralstonia metallidurans (strain CH34 / ATCC 43123 / DSM 2839)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 251426.00

構造登録者

Jost, M.,Drennan, C.L. (登録日: 2015-07-15, 公開日: 2015-09-09, 最終更新日: 2023-09-27)

主引用文献

Jost, M.,Born, D.A.,Cracan, V.,Banerjee, R.,Drennan, C.L.
Structural Basis for Substrate Specificity in Adenosylcobalamin-dependent Isobutyryl-CoA Mutase and Related Acyl-CoA Mutases.
J.Biol.Chem., 290:26882-26898, 2015

PubMed 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 efforts for biotechnological applications ranging from production of biofuels and commercial products to hydrocarbon remediation.

PubMed: 26318610
DOI: 10.1074/jbc.M115.676890

実験手法

X-RAY DIFFRACTION (3.5 Å)