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Experimental study of hydrogen bonding potentially stabilizing the 5'-Deoxyadenosyl radical from coenzyme B12


Friedrich, Peter; Baisch, Ulrich; Harrington, Ross W; Lyatuu, Fredrick; Zhou, Kai; Zelder, Felix; McFarlane, William; Buckel, Wolfgang; Golding, Bernard T (2012). Experimental study of hydrogen bonding potentially stabilizing the 5'-Deoxyadenosyl radical from coenzyme B12. Chemistry - A European Journal, 18(50):16114-16122.

Abstract

Coenzyme B12 can assist radical enzymes that accomplish the vicinal interchange of a hydrogen atom with a functional group. It has been proposed that the Co?C bond homolysis of coenzyme B12 to cob(II)alamin and the 5'-deoxyadenosyl radical is aided by hydrogen bonding of the corrin C19?H to the 3'-O of the ribose moiety of the incipient 5'-deoxyadenosyl radical, which is stabilized by 30 kJ?mol-1 (B. Durbeej et al., Chem. Eur. J. 2009, 15, 85788585). The diastereoisomers (R)- and (S)-2,3-dihydroxypropylcobalamin were used as models for coenzyme B12. A downfield shift of the NMR signal for the C19?H proton was observed for the (R)-isomer (delta=4.45 versus 4.01 ppm for the (S)-isomer) and can be ascribed to an intramolecular hydrogen bond between the C19?H and the oxygen of CHOH. Crystal structures of (R)- and (S)-2,3-dihydroxypropylcobalamin showed C19?H center dot center dot center dot O distances of 3.214(7) angstrom angstrom(R-isomer) and 3.281(11) angstrom (S-isomer), which suggest weak hydrogen-bond interactions (-Delta G<6 kJ?mol-1) between the CHOH of the dihydroxypropyl ligand and the C19?H. Exchange of the C19?H, which is dependent on the cobalt redox state, was investigated with cob(I)alamin, cob(II)alamin, and cob(III)alamin by using NMR spectroscopy to monitor the uptake of deuterium from deuterated water in the pH range 311. No exchange was found for any of the cobalt oxidation states. 3',5'-Dideoxyadenosylcobalamin, but not the 2',5'-isomer, was found to act as a coenzyme for glutamate mutase, with a 15-fold lower kcat/KM than 5'-deoxyadenosylcobalamin. This indicates that stabilization of the 5'-deoxyadenosyl radical by a hydrogen bond that involves the C19?H and the 3'-OH group of the cofactor is, at most, 7 kJ?mol-1 (Delta G). Examination of the crystal structure of glutamate mutase revealed additional stabilizing factors: hydrogen bonds between both the 2'-OH and 3'-OH groups and glutamate 330. The actual strength of a hydrogen bond between the C19?H and the 3'-O of the ribose moiety of the 5'-deoxyadenosyl group is concluded not to exceed 6 kJ?mol-1 (-Delta G).

Abstract

Coenzyme B12 can assist radical enzymes that accomplish the vicinal interchange of a hydrogen atom with a functional group. It has been proposed that the Co?C bond homolysis of coenzyme B12 to cob(II)alamin and the 5'-deoxyadenosyl radical is aided by hydrogen bonding of the corrin C19?H to the 3'-O of the ribose moiety of the incipient 5'-deoxyadenosyl radical, which is stabilized by 30 kJ?mol-1 (B. Durbeej et al., Chem. Eur. J. 2009, 15, 85788585). The diastereoisomers (R)- and (S)-2,3-dihydroxypropylcobalamin were used as models for coenzyme B12. A downfield shift of the NMR signal for the C19?H proton was observed for the (R)-isomer (delta=4.45 versus 4.01 ppm for the (S)-isomer) and can be ascribed to an intramolecular hydrogen bond between the C19?H and the oxygen of CHOH. Crystal structures of (R)- and (S)-2,3-dihydroxypropylcobalamin showed C19?H center dot center dot center dot O distances of 3.214(7) angstrom angstrom(R-isomer) and 3.281(11) angstrom (S-isomer), which suggest weak hydrogen-bond interactions (-Delta G<6 kJ?mol-1) between the CHOH of the dihydroxypropyl ligand and the C19?H. Exchange of the C19?H, which is dependent on the cobalt redox state, was investigated with cob(I)alamin, cob(II)alamin, and cob(III)alamin by using NMR spectroscopy to monitor the uptake of deuterium from deuterated water in the pH range 311. No exchange was found for any of the cobalt oxidation states. 3',5'-Dideoxyadenosylcobalamin, but not the 2',5'-isomer, was found to act as a coenzyme for glutamate mutase, with a 15-fold lower kcat/KM than 5'-deoxyadenosylcobalamin. This indicates that stabilization of the 5'-deoxyadenosyl radical by a hydrogen bond that involves the C19?H and the 3'-OH group of the cofactor is, at most, 7 kJ?mol-1 (Delta G). Examination of the crystal structure of glutamate mutase revealed additional stabilizing factors: hydrogen bonds between both the 2'-OH and 3'-OH groups and glutamate 330. The actual strength of a hydrogen bond between the C19?H and the 3'-O of the ribose moiety of the 5'-deoxyadenosyl group is concluded not to exceed 6 kJ?mol-1 (-Delta G).

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Language:English
Date:2012
Deposited On:04 Mar 2013 14:02
Last Modified:05 Apr 2016 16:35
Publisher:Wiley-VCH Verlag Berlin
ISSN:0947-6539
Publisher DOI:https://doi.org/10.1002/chem.201201840

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