Structure of the 5,6-Dimethylbenzimidazolylcobamide Coenzyme

Lenhert, P. G.; Hodgkin, Dorothy Crowfoot

doi:10.1038/192937a0

Cited by 318 publications

(159 citation statements)

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“…A well resolved X‐ray crystal structure was obtained for AdoRbl, which is the first of any metal analogue of the Cbl series. It confirmed the NMR‐derived chemical constitution of AdoRbl and showed basic structural features similar to those of AdoCbl11 (Figure 4 and Figure S6). As in AdoCbl, the Ado group of AdoRbl is positioned roughly above ring C of the corrin ring.…”

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confidence: 72%

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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confidence: 72%

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

et al. 2016

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“…They act as essential cofactors of a defined set of enzymes that are either mutases, eliminases, methyltransferases, or reductive dehalogenases (2,3). Cobamides share a complex core structure, the corrin ring, which is a unique contracted tetrapyrrole ring system that binds a central cobalt ion (4). When the cobalt ion is in its Co 3ϩ oxidation state, it binds two additional ligands.…”

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The SMUL_1544 Gene Product Governs Norcobamide Biosynthesis in the Tetrachloroethene-Respiring Bacterium Sulfurospirillum multivorans

et al. 2016

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The tetrachloroethene (PCE)-respiring bacterium Sulfurospirillum multivorans produces a unique cobamide, namely, norpseudo-B 12 , which, in comparison to other cobamides, e.g., cobalamin and pseudo-B 12 , lacks the methyl group in the linker moiety of the nucleotide loop. In this study, the protein SMUL_1544 was shown to be responsible for the formation of the unusual linker moiety, which is most probably derived from ethanolamine-phosphate (EA-P) as the precursor. The product of the SMUL_1544 gene successfully complemented a Salmonella enterica ⌬cobD mutant. The cobD gene encodes an L-threonine-O-3-phosphate (L-Thr-P) decarboxylase responsible for the synthesis of (R)-1-aminopropan-2-ol O-2-phosphate (AP-P), required specifically for cobamide biosynthesis. When SMUL_1544 was produced in the heterologous host lacking CobD, norpseudo-B 12 was formed, which pointed toward the formation of EA-P rather than AP-P. Guided cobamide biosynthesis experiments with minimal medium supplemented with L-Thr-P supported cobamide biosynthesis in S. enterica producing SMUL_1544 or S. multivorans. Under these conditions, both microorganisms synthesized pseudo-B 12 . This observation indicated a flexibility in the SMUL_1544 substrate spectrum.

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“…Later Galen Lenhert showed in Dorothy's laboratory that the coenzyme contains a cobalt-carbon bond, making it the first known naturally occurring biologically significant organometallic compound (Lenhert & Hodgkin, 1961). The early work on vitamin BIZ was done with June Broomhead Lindsey, Clara Brink Shoemaker, Jennifer Harrison Kamper, Ken Trueblood, John H. Robertson, Maureen Mackay, myself, John White at Princeton University, and many others.…”

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confidence: 99%

Dorothy crowfoot hodgkin (1910–1994)

Glusker

1994

Protein Science

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Structure of the 5,6-Dimethylbenzimidazolylcobamide Coenzyme

Cited by 318 publications

References 4 publications

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

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

The SMUL_1544 Gene Product Governs Norcobamide Biosynthesis in the Tetrachloroethene-Respiring Bacterium Sulfurospirillum multivorans

Dorothy crowfoot hodgkin (1910–1994)

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Structure of the 5,6-Dimethylbenzimidazolylcobamide Coenzyme

Cited by 318 publications

References 4 publications

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

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

The SMUL_1544 Gene Product Governs Norcobamide Biosynthesis in the Tetrachloroethene-Respiring Bacterium Sulfurospirillum multivorans

Dorothy crowfoot hodgkin (1910–1994)

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

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