Spectroscopic and computational studies on the adenosylcobalamin-dependent methylmalonyl-CoA mutase: evaluation of enzymatic contributions to Co-C bond activation in the Co3+ ground state.

Journal of the American Chemical Society
Amanda J BrooksThomas C Brunold

Abstract

Methylmalonyl-CoA mutase (MMCM) is an enzyme that utilizes the adenosylcobalamin (AdoCbl) cofactor to catalyze the rearrangement of methylmalonyl-CoA to succinyl-CoA. Despite many years of dedicated research, the mechanism by which MMCM and related AdoCbl-dependent enzymes accelerate the rate for homolytic cleavage of the cofactor's Co-C bond by approximately 12 orders of magnitude while avoiding potentially harmful side reactions remains one of the greatest subjects of debate among B(12) researchers. In this study, we have employed electronic absorption (Abs) and magnetic circular dichroism (MCD) spectroscopic techniques to probe cofactor/enzyme active site interactions in the Co(3+)Cbl "ground" state for MMCM reconstituted with both the native cofactor AdoCbl and its derivative methylcobalamin (MeCbl). In both cases, Abs and MCD spectra of the free and enzyme-bound cofactor are very similar, indicating that replacement of the intramolecular base 5,6-dimethylbenzimidazole (DMB) by a histidine residue from the enzyme active site has insignificant effects on the cofactor's electronic properties. Likewise, spectral perturbations associated with substrate (analogue) binding to holo-MMCM are minor, arguing against substrate-induced...Continue Reading

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Citations

Apr 13, 2006·Journal of the American Chemical Society·Troy A StichThomas C Brunold
Mar 26, 2008·The Journal of Chemical Physics·Dmitry Ganyushin, Frank Neese
Dec 3, 2008·The Journal of Chemical Physics·Tadeusz AndruniówPawel M Kozlowski
Jun 5, 2012·Journal of Zhejiang University. Science. B·Tóshiko Takahashi-IñiguezMaría Elena Flores
Feb 17, 2006·Dalton Transactions : an International Journal of Inorganic Chemistry·Kenneth L Brown
Nov 9, 2012·Natural Product Reports·Refaat B HamedChristopher J Schofield
May 4, 2017·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Alex R Jones
Apr 23, 2017·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Koji OohoraTakashi Hayashi
Apr 21, 2009·The Journal of Physical Chemistry. B·Piotr LodowskiPawel M Kozlowski
Sep 15, 2009·Chemical Reviews·Israel FernándezMiguel A Sierra
Aug 10, 2006·Chemical Reviews·Perry A FreyGeorge H Reed
Jul 21, 2006·The Journal of Physical Chemistry. B·Roseanne J SensionE Neil G Marsh
Sep 14, 2013·Journal of the American Chemical Society·Miao Wang, Kurt Warncke
May 10, 2012·The Journal of Physical Chemistry. a·Azaria S EisenbergRonald L Birke
May 23, 2014·Biochemistry·Elizabeth BrunkUrsula Rothlisberger
Jul 9, 2014·Inorganic Chemistry·Ivan G Pallares, Thomas C Brunold
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Feb 9, 2019·The Journal of Physical Chemistry. B·Neeraj KumarPawel M Kozlowski
Sep 1, 2005·Journal of the American Chemical Society·Xiaohua LiuXiaoming Feng
Nov 16, 2005·Biochemistry·Amanda J BrooksThomas C Brunold
Jan 6, 2005·Journal of the American Chemical Society·Derek A Pratt, Wilfred A van der Donk
Nov 25, 2005·Journal of the American Chemical Society·Amanda J BrooksThomas C Brunold
Jun 23, 2005·Journal of the American Chemical Society·Kasper P Jensen, Ulf Ryde

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