TY - JOUR
T1 - Multielectron Chemistry within a Model Nickel Metalloprotein
T2 - Mechanistic Implications for Acetyl-CoA Synthase
AU - Manesis, Anastasia C.
AU - O'Connor, Matthew J.
AU - Schneider, Camille R.
AU - Shafaat, Hannah S.
N1 - Funding Information:
This work has been supported by the OSU Department of Chemistry and Biochemistry and the ACS PRF Fund (57403-DNI6). C.R.S. acknowledges support from an NIH Chemistry-Biology Training Grant (GM-08512) and M.J.O. acknowledges the OSU College of Arts and Sciences Honors Undergraduate Research Scholarship.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/8/2
Y1 - 2017/8/2
N2 - The acetyl coenzyme A synthase (ACS) enzyme plays a central role in the metabolism of anaerobic bacteria and archaea, catalyzing the reversible synthesis of acetyl-CoA from CO and a methyl group through a series of nickel-based organometallic intermediates. Owing to the extreme complexity of the native enzyme systems, the mechanism by which this catalysis occurs remains poorly understood. In this work, we have developed a protein-based model for the NiP center of acetyl coenzyme A synthase using a nickel-substituted azurin protein (NiAz). NiAz is the first model nickel protein system capable of accessing three (NiI/NiII/NiIII) distinct oxidation states within a physiological potential range in aqueous solution, a critical feature for achieving organometallic ACS activity, and binds CO and -CH3 groups with biologically relevant affinity. Characterization of the NiI-CO species through spectroscopic and computational techniques reveals fundamentally similar features between the model NiAz system and the native ACS enzyme, highlighting the potential for related reactivity in this model protein. This work provides insight into the enzymatic process, with implications toward engineering biological catalysts for organometallic processes.
AB - The acetyl coenzyme A synthase (ACS) enzyme plays a central role in the metabolism of anaerobic bacteria and archaea, catalyzing the reversible synthesis of acetyl-CoA from CO and a methyl group through a series of nickel-based organometallic intermediates. Owing to the extreme complexity of the native enzyme systems, the mechanism by which this catalysis occurs remains poorly understood. In this work, we have developed a protein-based model for the NiP center of acetyl coenzyme A synthase using a nickel-substituted azurin protein (NiAz). NiAz is the first model nickel protein system capable of accessing three (NiI/NiII/NiIII) distinct oxidation states within a physiological potential range in aqueous solution, a critical feature for achieving organometallic ACS activity, and binds CO and -CH3 groups with biologically relevant affinity. Characterization of the NiI-CO species through spectroscopic and computational techniques reveals fundamentally similar features between the model NiAz system and the native ACS enzyme, highlighting the potential for related reactivity in this model protein. This work provides insight into the enzymatic process, with implications toward engineering biological catalysts for organometallic processes.
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U2 - 10.1021/jacs.7b03892
DO - 10.1021/jacs.7b03892
M3 - Article
C2 - 28675928
AN - SCOPUS:85026803513
SN - 0002-7863
VL - 139
SP - 10328
EP - 10338
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 30
ER -