“…Coenzyme B 12 , which is also known as adenosylcobalamin (AdoCbl1), provides one of very few known examples of a bio-organometallic species (1). AdoCbl contains a cobalt(III) ion that is equatorially ligated by four nitrogens of a tetrapyrrole macrocycle, termed the corrin ring, and axially coordinated by the 5′-carbon atom of an adenosyl (Ado) moiety on the “upper” face and a nitrogen atom from 5,6-dimethylimidazole (DMB) on the “lower” face (Figure 1) (2).…”
The PduO-type ATP:corrinoid adenosyltransferase from Lactobacillus reuteri (LrPduO) catalyzes the formation of the essential Co–C bond of adenosylcobalamin (coenzyme B12) by transferring the adenosyl group from co-substrate ATP to a transient Co1+corrinoid species generated in the enzyme active site. While PduO-type enzymes have previously been believed to be capable of adenosylating only Co1+cobalamin (Co1+Cbl−), our kinetic data obtained in this study provide in vitro evidence that LrPduO can in fact also utilize the incomplete corrinoid Co1+cobinamide (Co1+Cbi) as an alternative substrate. To explore the mechanism by which LrPduO overcomes the thermodynamically challenging reduction of its Co2+corrinoid substrates, we have examined how the enzyme active site alters the geometric and electronic properties of Co2+Cbl and Co2+Cbi+ by using electronic absorption, magnetic circular dichroism, and electron paramagnetic resonance spectroscopic techniques. Our data reveal that upon binding to LrPduO that was pre-incubated with ATP, both Co2+corrinoids undergo a partial (~40–50%) conversion to distinct paramagnetic Co2+species. The spectroscopic signatures of these species are consistent with essentially four-coordinate, square-planar Co2+ complexes, based on a comparison with the results obtained in our previous studies of related enzymes. Consequently, it appears that the general strategy employed by adenosyltransferases for effecting Co2+→Co1+ reduction involves the formation of an “activated” Co2+corrinoid intermediate that lacks any significant axial bonding interactions, so as to stabilize the redox-active, Co 3dz2-based molecular orbital.
“…Coenzyme B 12 , which is also known as adenosylcobalamin (AdoCbl1), provides one of very few known examples of a bio-organometallic species (1). AdoCbl contains a cobalt(III) ion that is equatorially ligated by four nitrogens of a tetrapyrrole macrocycle, termed the corrin ring, and axially coordinated by the 5′-carbon atom of an adenosyl (Ado) moiety on the “upper” face and a nitrogen atom from 5,6-dimethylimidazole (DMB) on the “lower” face (Figure 1) (2).…”
The PduO-type ATP:corrinoid adenosyltransferase from Lactobacillus reuteri (LrPduO) catalyzes the formation of the essential Co–C bond of adenosylcobalamin (coenzyme B12) by transferring the adenosyl group from co-substrate ATP to a transient Co1+corrinoid species generated in the enzyme active site. While PduO-type enzymes have previously been believed to be capable of adenosylating only Co1+cobalamin (Co1+Cbl−), our kinetic data obtained in this study provide in vitro evidence that LrPduO can in fact also utilize the incomplete corrinoid Co1+cobinamide (Co1+Cbi) as an alternative substrate. To explore the mechanism by which LrPduO overcomes the thermodynamically challenging reduction of its Co2+corrinoid substrates, we have examined how the enzyme active site alters the geometric and electronic properties of Co2+Cbl and Co2+Cbi+ by using electronic absorption, magnetic circular dichroism, and electron paramagnetic resonance spectroscopic techniques. Our data reveal that upon binding to LrPduO that was pre-incubated with ATP, both Co2+corrinoids undergo a partial (~40–50%) conversion to distinct paramagnetic Co2+species. The spectroscopic signatures of these species are consistent with essentially four-coordinate, square-planar Co2+ complexes, based on a comparison with the results obtained in our previous studies of related enzymes. Consequently, it appears that the general strategy employed by adenosyltransferases for effecting Co2+→Co1+ reduction involves the formation of an “activated” Co2+corrinoid intermediate that lacks any significant axial bonding interactions, so as to stabilize the redox-active, Co 3dz2-based molecular orbital.
“…The susceptibility of [2] + to nucleophilic attack is reminiscent of Co( iii )-alkyls as represented by vitamin B 12 and its derivatives and models. 33,34 Given the vast chemistry of B 12 mimics, it is possible that a wide range of diiron alkyl chemistry awaits discovery and development.…”
“…The colors of the three cobalamin coordination states also depend on the concentration and range, for example, for cob(I)alamin between black and light green. Thermodynamically, the cobalt center of cobalamins is stabilized against cob(III)alamin/cob(II)alamin reduction by strongly nucleophilic, coordinating, or basic ligands ( Butler and Kräutler, 2006 ). Hence, the values for reduction potentials for cob(III)alamin/cob(II)alamin redox couples are greater for the base-on form in comparison with the base-off forms of cobalamins.…”
Section: Biochemical Characterization Of the Mmachc Proteinmentioning
confidence: 99%
“…The redox potential of cob(II)alamin base-on /cob(I)alamin and cob(II)alamin base-off /cob(I)alamin have been reported to be −0.61 V and −0.50 V (both values vs NHE, 22°C), respectively ( Figure 4 ) ( Lexa and Saveant, 1976 ). Figure 4 Shuttling of cobalamins between the cob(III)alamin, cob(II)alamin, and cob(I)alamin redox states (∗versus NHE, 22°C) Adapted from Butler and Kräutler (2006) …”
Section: Biochemical Characterization Of the Mmachc Proteinmentioning
confidence: 99%
“…The pseudo-pentacoordinated cob(I)alamin transition state is more thermodynamically favorable than a tetracoordinated cob(I)alamin ( Kumar et al., 2012 ; Kumar and Kozlowski, 2011 ). Trends in the redox transformation of cobalamins have been extensively studied and reviewed elsewhere ( Butler and Kräutler, 2006 ; Dereven’kov et al., 2016 ; Johns et al., 2015 ; Lehene et al., 2021 ; Lexa and Saveant, 1976 ; Pugina et al., 2018 ; Salnikov et al., 2021 ).…”
Section: Biochemical Characterization Of the Mmachc Proteinmentioning
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