The novel structure and chemistry of iron–sulfur clusters in the adenosylmethionine-dependent radical enzyme biotin synthase

Jarrett, Joseph T.

doi:10.1016/j.abb.2004.10.003

Cited by 74 publications

(68 citation statements)

References 52 publications

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“…4A was that the amount of iron bound to the cluster mutants of Bio2 was variable. This fact might result from the different sensitivities of the 2Fe/2S and 4Fe/4S clusters towards contact with air and towards reducing conditions (25), as well as from a possible partial retention of the 2Fe/2S cluster after removal of only one of its cysteine ligands (19). Nevertheless, all forms of Bio2 tested here did not significantly differ in their iron content depending on the presence or absence of the Isa proteins.…”

mentioning

confidence: 58%

“…Although the sulfur donor for this reaction is still under debate, current evidence strongly implicates the 2Fe/2S cluster of biotin synthase as the source of biotin sulfur (2). Thus, biotin synthase may behave like a reactant which requires the repair of the 2Fe/2S cofactor for subsequent reaction cycles (25). The mitochondrial localization of Bio2 necessitates that all reactants required in vivo have to be present in mitochondria.…”

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confidence: 99%

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The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

et al. 2007

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The yeast Saccharomyces cerevisiae is able to use some biotin precursors for biotin biosynthesis. Insertion of a sulfur atom into desthiobiotin, the final step in the biosynthetic pathway, is catalyzed by biotin synthase (Bio2). This mitochondrial protein contains two iron-sulfur (Fe/S) clusters that catalyze the reaction and are thought to act as a sulfur donor. To identify new components of biotin metabolism, we performed a genetic screen and found that Isa2, a mitochondrial protein involved in the formation of Fe/S proteins, is necessary for the conversion of desthiobiotin to biotin. Depletion of Isa2 or the related Isa1, however, did not prevent the de novo synthesis of any of the two Fe/S centers of Bio2. In contrast, Fe/S cluster assembly on Bio2 strongly depended on the Isu1 and Isu2 proteins. Both isa mutants contained low levels of Bio2. This phenotype was also found in other mutants impaired in mitochondrial Fe/S protein assembly and in wild-type cells grown under iron limitation. Low Bio2 levels, however, did not cause the inability of isa mutants to utilize desthiobiotin, since this defect was not cured by overexpression of BIO2. Thus, the Isa proteins are crucial for the in vivo function of biotin synthase but not for the de novo synthesis of its Fe/S clusters. Our data demonstrate that the Isa proteins are essential for the catalytic activity of Bio2 in vivo.

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confidence: 58%

mentioning

confidence: 99%

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

et al. 2007

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“…For many years one of the few points of agreement in the literature was the finding that BioB itself is the sulfur source impinges, that the BioB reaction is not catalytic in vitro (57,59,68). Numerous and diverse justifications were put forth for the observed lack of catalysis (69-71), but no general agreement emerged.…”

Section: Biobmentioning

confidence: 86%

“…As mentioned above lipoic acid synthase is a member of the radical-SAM enzyme superfamily which utilize a reduced iron-sulfur cluster and SAM to generate 5'-deoxyadenosyl 5′-radicals (5′-dA) for further radical-based chemistry (59,(243)(244)(245)(246). In the lipoic acid synthase reaction (Fig.…”

Section: Lipoic Acid Synthesis Proceeds By An Unexpected and Extraordmentioning

confidence: 99%

Biotin and Lipoic Acid: Synthesis, Attachment, and Regulation

Cronan

2008

EcoSal Plus

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SummaryTwo vitamins, biotin and lipoic acid, are essential in all three domains of life. Both coenzymes function only when covalently attached to key metabolic enzymes. There they act as "swinging arms" that shuttle intermediates between two active sites (= covalent substrate channeling) of key metabolic enzymes. Although biotin was discovered over 100 years ago and lipoic acid 60 years ago, it was not known how either coenzyme is made until recently. In Escherichia coli the synthetic pathways for both coenzymes have now been worked out for the first time.The late steps of biotin synthesis, those involved in assembling the fused rings, were welldescribed biochemically years ago, although recent progress has been made on the BioB reaction, the last step of the pathway in which the biotin sulfur moiety is inserted. In contrast, the early steps of biotin synthesis, assembly of the fatty acid-like "arm" of biotin were unknown. It has now been demonstrated that the arm is made by using disguised substrates to gain entry into the fatty acid synthesis pathway followed by removal of the disguise when the proper chain length is attained. The BioC methyltransferase is responsible for introducing the disguise and the BioH esterase for its removal.In contrast to biotin, which is attached to its cognate proteins as a finished molecule, lipoic acid is assembled on its cognate proteins. An octanoyl moiety is transferred from the octanoyl-ACP of fatty acid synthesis to a specific lysine residue of a cognate protein by the LipB octanoyl transferase followed by sulfur insertion at carbons C6 and C8 by the LipA lipoyl synthetase. Assembly on the cognate proteins regulates the amount of lipoic acid synthesized and thus there is no transcriptional control of the synthetic genes. In contrast transcriptional control of the biotin synthetic genes is wielded by a remarkably sophisticated, yet simple, system, exerted through BirA a dual function protein that both represses biotin operon transcription and ligates biotin to its cognate protein.

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“…For instance, the electron transfer problem includes also the role of mixed valence feredoxin compounds, which participate in electron transfer [103][104][105] to a series of biosystems and participate into turn-over of cobalamin-dependent enzyme processes. The mixed valence feredoxin compounds are a common example of vibronic (Jahn-Teller) systems in chemistry, due to their symmetry.…”

Section: The Multi-confi Guration Effects In Methylcob(ii)alamin and mentioning

confidence: 99%

The Nature of the Co-C Bond Cleavage Processes in Methylcob(II)Alamin and Adenosylcob(III)Alamin

Spataru¹,

Fernández²

2016

ChemJMold

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Abstract. Unfortunately, there are still signifi cant disagreements between experimental and theoretical data of rate constants, energy barriers for Co-C bond cleavage process and coordination numbers of vitamin B 12 coenzyme species in spite of the remarkable efforts done by research community. Therefore, no grounded mechanisms for Co-C vitamin B 12 coenzyme bond breaking process and subsequent reactions have been found up to now. The infl uence of the mixing orbitals e.g. Pseudo-Jahn-Teller and similar effects on the reactions paths of bond-cleavage mechanisms of vitamin B 12 co-factors must be taken into account by utilizing multi-reference methods, in particular multiconfi gurational self-consistent fi eld (MCSCF) method. Then, the change in total energy along the normal coordinate Q for the stretching mode including Co-C and Co-N bonds in vitamin B 12 cofactors is expected due to a "vibronic" coupling term, which couples an excited state and ground state by a second order derivative potential-energy operator. The strong state mixing effect is expected to lead to low energy barriers and to Co-C and Co-N axial bond cleavage events in agreement with experimental data. Afterward, the updated mechanisms of vitamin B 12 bio-processes can be determined.Keywords: vitamin B 12 , mechanism, bio-catalysis, Pseudo-Jahn-Teller effect, DFT, MCSCF. Received: December 2015/ Revised fi nal: February 2016/ Accepted: February 2016 IntroductionVitamin B 12 cofactor is one of eight B vitamins and is involved in mammalian cellular metabolism, infl uencing amino acid and DNA synthesis [1] and hematopoiesis. The best known human physiological function of vitamin B 12 is its role in promoting normal health in the brain and nervous system. Vitamin B 12 anemia can cause such neurologic dysfunction as weakness, fatigue, light-headedness, rapid heartbeat, rapid breathing, pale skin color, bruising, and bleeding (including bleeding gums). The more severe vitamin B 12 anemia dysfunctions are characterized by tingling or numbness of the fi ngers and toes, diffi culty walking, mood changes, depression, memory loss, disorientation and, in most severe cases, dementia [2]. Vitamin B 12 defi ciency has even been considered in playing a role in the development of Alzheimer's disease [3][4][5][6][7].The vitamin B 12 cofactor contains a cobalt atom surrounded by an equatorial corrin ring. Covalently linked to the central atom is a dimethylbenzimidazole that occupies one of the axial coordination positions. The opposite coordinate is available for several ligands in bio-medium or in solution; however, known biologically active structures containing adenosyl-or methyl have been considered most often (Figure 1).

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The novel structure and chemistry of iron–sulfur clusters in the adenosylmethionine-dependent radical enzyme biotin synthase

Cited by 74 publications

References 52 publications

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

Biotin and Lipoic Acid: Synthesis, Attachment, and Regulation

The Nature of the Co-C Bond Cleavage Processes in Methylcob(II)Alamin and Adenosylcob(III)Alamin

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