TY - JOUR
T1 - Visualizing the reaction cycle in an Iron(II)- and 2-(Oxo)-glutarate-dependent hydroxylase
AU - Mitchell, Andrew J.
AU - Dunham, Noah P.
AU - Martinie, Ryan J.
AU - Bergman, Jonathan A.
AU - Pollock, Christopher J.
AU - Hu, Kai
AU - Allen, Benjamin D.
AU - Chang, Wei Chen
AU - Silakov, Alexey
AU - Bollinger, J. Martin
AU - Krebs, Carsten
AU - Boal, Amie K.
N1 - Funding Information:
This work was supported by the National Institutes of Health (GM119707 to A.K.B. and GM113106 to J.M.B. and C.K.), a National Science Foundation Graduate Research Fellowship Program (Grant No. DGE1255832) to R.J.M, and an NIH National Research Service Award to C.J.P. (GM113389). We gratefully acknowledge the resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357. Use of the LS-CAT Sector 21 was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor (Grant 085P1000817). GM/CA@APS has been funded in whole or in part with Federal funds from the National Cancer Institute (ACB-12002) and the National Institute of General Medical Sciences (AGM-12006). The Eiger 16M detector was funded by an NIH-Office of Research Infrastructure Programs, High-End Instrumentation Grant (1S10OD012289-01A1).
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/10/4
Y1 - 2017/10/4
N2 - Iron(II)- and 2-(oxo)-glutarate-dependent oxygenases catalyze diverse oxidative transformations that are often initiated by abstraction of hydrogen from carbon by iron(IV)-oxo (ferryl) complexes. Control of the relative orientation of the substrate C-H and ferryl Fe-O bonds, primarily by direction of the oxo group into one of two cisrelated coordination sites (termed inline and offline), may be generally important for control of the reaction outcome. Neither the ferryl complexes nor their fleeting precursors have been crystallographically characterized, hindering direct experimental validation of the offline hypothesis and elucidation of the means by which the protein might dictate an alternative oxo position. Comparison of high-resolution X-ray crystal structures of the substrate complex, an Fe(II)-peroxysuccinate ferryl precursor, and a vanadium(IV)-oxo mimic of the ferryl intermediate in the L-arginine 3-hydroxylase, VioC, reveals coordinated motions of active site residues that appear to control the intermediate geometries to determine reaction outcome.
AB - Iron(II)- and 2-(oxo)-glutarate-dependent oxygenases catalyze diverse oxidative transformations that are often initiated by abstraction of hydrogen from carbon by iron(IV)-oxo (ferryl) complexes. Control of the relative orientation of the substrate C-H and ferryl Fe-O bonds, primarily by direction of the oxo group into one of two cisrelated coordination sites (termed inline and offline), may be generally important for control of the reaction outcome. Neither the ferryl complexes nor their fleeting precursors have been crystallographically characterized, hindering direct experimental validation of the offline hypothesis and elucidation of the means by which the protein might dictate an alternative oxo position. Comparison of high-resolution X-ray crystal structures of the substrate complex, an Fe(II)-peroxysuccinate ferryl precursor, and a vanadium(IV)-oxo mimic of the ferryl intermediate in the L-arginine 3-hydroxylase, VioC, reveals coordinated motions of active site residues that appear to control the intermediate geometries to determine reaction outcome.
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U2 - 10.1021/jacs.7b07374
DO - 10.1021/jacs.7b07374
M3 - Article
C2 - 28823155
AN - SCOPUS:85032628383
SN - 0002-7863
VL - 139
SP - 13830
EP - 13836
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 39
ER -