Accurate Redetermination of the X-ray Structure and Electronic Bonding in Adenosylcobalamin

Ouyang, Lizhi; Rulis, Paul; Ching, W. Y.; Nardin, Giorgio; Randaccio, Lucio

doi:10.1021/ic0348446

Cited by 86 publications

(107 citation statements)

References 35 publications

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“…29 The DFT calculations employing the B3LYP functional do not capture the trend which is experimentally observed for axial bond distances in AdoCbl 29 and MeCbl 37 cofactors. This most likely reflects structural simplifications introduced by truncating the AdoCbl side chains and replacing the dimethylbenzimidazole ligand with imidazole.…”

Section: Adenosyl Corrinsmentioning

confidence: 82%

DFT Analysis of Co−Alkyl and Co−Adenosyl Vibrational Modes in B₁₂-Cofactors

et al. 2006

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Density functional theory (DFT)-based normal mode calculations have been carried out on models for B 12 -cofactors to assign reported isotope-edited resonance Raman spectra, which isolate vibrations of the organo-Co group. Interpretation is straightforward for alkyl-Co derivatives, which display prominent Co-C stretching vibrational bands. DFT correctly reproduces Co-C distances and frequencies for the methyl and ethyl derivatives. However, spectra are complex for adenosyl derivatives, due to mixing of Co-C stretching with a ribose deformation coordinate and to activation of modes involving Co-C-C bending and Co-adenosyl torsion. Despite this complexity, the computed spectra provide a satisfactory re-assignment of the experimental data. Reported trends in adenosyl-cobalamin spectra upon binding to the methylmalonyl CoA mutase enzyme, as well as on subsequent binding of substrates and inhibitors, provide support for an activation mechanism involving substrate-induced deformation of the adenosyl ligand.

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Section: Adenosyl Corrinsmentioning

confidence: 82%

DFT Analysis of Co−Alkyl and Co−Adenosyl Vibrational Modes in B₁₂-Cofactors

et al. 2006

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“…Separation proceeded with a flow rate of 5 mL min −1 , isocratically at 95% H 2 O/5% CH 3 CN. After elution of the nucleoside, successive washes with 95% CH 3 Samples of photolyzed adenosylcobalamin were co-injected with commercial standards. Only two standards, adenine and adenosine, co-migrated with minor peaks found in the photolysis reaction mixture.…”

Section: Characterization Of Nucleosidesmentioning

confidence: 99%

“…Over time, the initial cob(III)alamin-related spectrum decays, nearly quantitatively, to that of cob(III)alamin (---). 3 The decay occurs in a biphasic manner, with a rapid change over ca. 30 minutes and a subsequent slower decay over a period of nearly 20 h (Figure 3A, inset).…”

Section: Transformation Of 5′-peroxyadenosine Into Adenosine-5′-aldehydementioning

confidence: 99%

5‘-Peroxyadenosine and 5‘-Peroxyadenosylcobalamin as Intermediates in the Aerobic Photolysis of Adenosylcobalamin

Schwartz

Frey

2007

Biochemistry

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The photolysis of adenosylcobalamin (coenzyme B 12 ) results in homolytic cleavage of the Co-C5′ bond, forming cob(II)alamin and the 5′-deoxyadenosyl radical. In the presence of molecular oxygen, it has been proposed that the primary reaction is interception of the 5′-deoxyadenosyl radical by O 2 to form adenosine-5′-aldehyde as the product (Hogenkamp, H. P. C., Ladd, J. N., and Barker, H. A. (1962) J. Biol. Chem. 237, 1950-1952. 5′-Peroxyadenosine is here found to be the initial nucleoside product of this reaction and that it decomposes to adenosine-5′-aldehyde. Evidence indicates that 5′-peroxyadenosine arises from the hydrolysis of 5′-peroxyadenosylcobalamin, with the formation of cob(III)alamin. 5′-Peroxyadenosine undergoes further decomposition to adenosine-5′-aldehyde as the major final product of aerobic photolysis, as well as to adenosine and adenine as minor products. In a cobalamin-dependent process, 5′-peroxyadenosine becomes religated to cob(III)alamin to form 5′-peroxyadenosylcobalamin, which quickly decomposes to adenosine-5′-aldehyde and cob(III)alamin. This is supported by spectrophotometric observations of both rapidly photolyzed adenosylcobalamin and of the reaction of cob(III)alamin with excess 5′-peroxyadenosine. 5′-Peroxyadenosine also slowly undergoes cobalamin-independent decomposition to adenosine-5′-aldehyde and the minor products adenosine and adenine. The present study provides a detailed description of the products initially formed when aqueous, homolytically cleaved adenosylcobalamin reacts with molecular oxygen and of the behavior of those products subsequent to photolysis.Enzymes dependent upon the vitamin B 12 -coenzyme adenosylcobalamin 1 catalyze intriguingly diverse chemical reactions, including carbon-skeleton rearrangements, reductive heteroatom eliminations, and intramolecular 1,2-migrations of heteroatomic substituents; and they proceed by mechanisms involving organic free radicals as intermediates (1,2). Adenosylcobalamin incorporates a cobalt ion in an octahedral arrangement with the pyrroline and pyrrolidine groups of a corrin ring system making up the equatorial ligands, the nitrogen from a dimethylbenzimidazole moiety as the lower axial ligand, and a 5′-deoxadenosyl moiety forming a cobalt-carbon (Co-C5′) bond in the sixth, upper axial ligand position (3).The key to the function of adenosylcobalamin in enzymatic catalysis is the reversible homolytic scission of the Co-C5′ bond, generating cob(II)alamin and a transiently formed 5′- †

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“…Furthermore, the flatter corrin ligand of AdoRbl displays a record small fold angle of 5.9(2)° (13.3° in AdoCbl; see Figures 7, S8, and S9) 18. Ring B of AdoRbl exhibits a striking reversed conformational twist when compared to the structures of AdoCbl and other natural corrinoids.…”

mentioning

confidence: 94%

Total Synthesis, Structure, and Biological Activity of Adenosylrhodibalamin, the Non‐Natural Rhodium Homologue of Coenzyme B₁₂

et al. 2016

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B12 is unique among the vitamins as it is biosynthesized only by certain prokaryotes. The complexity of its synthesis relates to its distinctive cobalt corrin structure, which is essential for B12 biochemistry and renders coenzyme B12 (AdoCbl) so intriguingly suitable for enzymatic radical reactions. However, why is cobalt so fit for its role in B12‐dependent enzymes? To address this question, we considered the substitution of cobalt in AdoCbl with rhodium to generate the rhodium analogue 5′‐deoxy‐5′‐adenosylrhodibalamin (AdoRbl). AdoRbl was prepared by de novo total synthesis involving both biological and chemical steps. AdoRbl was found to be inactive in vivo in microbial bioassays for methionine synthase and acted as an in vitro inhibitor of an AdoCbl‐dependent diol dehydratase. Solution NMR studies of AdoRbl revealed a structure similar to that of AdoCbl. However, the crystal structure of AdoRbl revealed a conspicuously better fit of the corrin ligand for RhIII than for CoIII, challenging the current views concerning the evolution of corrins.

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Accurate Redetermination of the X-ray Structure and Electronic Bonding in Adenosylcobalamin

Cited by 86 publications

References 35 publications

DFT Analysis of Co−Alkyl and Co−Adenosyl Vibrational Modes in B₁₂-Cofactors

DFT Analysis of Co−Alkyl and Co−Adenosyl Vibrational Modes in B₁₂-Cofactors

5‘-Peroxyadenosine and 5‘-Peroxyadenosylcobalamin as Intermediates in the Aerobic Photolysis of Adenosylcobalamin

Total Synthesis, Structure, and Biological Activity of Adenosylrhodibalamin, the Non‐Natural Rhodium Homologue of Coenzyme B₁₂

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Accurate Redetermination of the X-ray Structure and Electronic Bonding in Adenosylcobalamin

Cited by 86 publications

References 35 publications

DFT Analysis of Co−Alkyl and Co−Adenosyl Vibrational Modes in B12-Cofactors

DFT Analysis of Co−Alkyl and Co−Adenosyl Vibrational Modes in B12-Cofactors

5‘-Peroxyadenosine and 5‘-Peroxyadenosylcobalamin as Intermediates in the Aerobic Photolysis of Adenosylcobalamin

Total Synthesis, Structure, and Biological Activity of Adenosylrhodibalamin, the Non‐Natural Rhodium Homologue of Coenzyme B12

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Product

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DFT Analysis of Co−Alkyl and Co−Adenosyl Vibrational Modes in B₁₂-Cofactors

DFT Analysis of Co−Alkyl and Co−Adenosyl Vibrational Modes in B₁₂-Cofactors

Total Synthesis, Structure, and Biological Activity of Adenosylrhodibalamin, the Non‐Natural Rhodium Homologue of Coenzyme B₁₂