4754-39-6Relevant articles and documents
Syntheses of potential antimetabolites. XV. Syntheses of a sulfonate analog of adenosine 5' phosphate and an alternative synthesis of 5', 8 S anhydroadenine nucleosides and 5' deoxyspongoadenosine and its isomers
Mizuno,Kaneko,Oikawa
, p. 1440 - 1444 (1974)
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Identification and characterization of functional homologs of nitrogenase cofactor biosynthesis protein NifB from methanogens
Fay, Aaron W.,Wiig, Jared A.,Lee, Chi Chung,Hu, Yilin
, p. 14829 - 14833 (2015)
Nitrogenase biosynthesis protein NifB catalyzes the radical S-adenosyl-L-methionine (SAM)-dependent insertion of carbide into the M cluster, the cofactor of the molybdenum nitrogenase from Azotobacter vinelandii. Here, we report the identification and characterization of two naturally €truncated€ homologs of NifB from Methanosarcina acetivorans (NifBMa) and Methanobacterium thermoautotrophicum (NifBMt), which contain a SAM-binding domain at the N terminus but lack a domain toward the C terminus that shares homology with NifX, an accessory protein in M cluster biosynthesis. NifBMa and NifBMt are monomeric proteins containing a SAM-binding [Fe4S4] cluster (designated the SAM cluster) and a [Fe4S4]-like cluster pair (designated the K cluster) that can be processed into an [Fe8S9] precursor to the M cluster (designated the L cluster). Further, the K clusters in NifBMa and NifBMt can be converted to L clusters upon addition of SAM, which corresponds to their ability to heterologously donate L clusters to the biosynthetic machinery of A. vinelandii for further maturation into the M clusters. Perhaps even more excitingly, NifBMa and NifBMt can catalyze the removal of methyl group from SAM and the abstraction of hydrogen from this methyl group by 5€-deoxyadenosyl radical that initiates the radical-based incorporation of methyl-derived carbide into the M cluster. The successful identification of NifBMa and NifBMt as functional homologs of NifB not only enabled classification of a new subset of radical SAM methyltransferases that specialize in complex metallocluster assembly, but also provided a new tool for further characterization of the distinctive, NifB-catalyzed methyl transfer and conversion to an iron-bound carbide.
Radical S-Adenosyl Methionine Enzyme BlsE Catalyzes a Radical-Mediated 1,2-Diol Dehydration during the Biosynthesis of Blasticidin S
Chen, Ridao,Feng, Jianqiang,Gao, Jin-Ming,Hou, Xueli,Lee, Yu-Hsuan,Liu, Hung-Wen,Liu, Xiao,Ruszczycky, Mark W.,Wang, Binju,Zhou, Jiahai
supporting information, p. 4478 - 4486 (2022/03/18)
The biosynthesis of blasticidin S has drawn attention due to the participation of the radical S-adenosyl methionine (SAM) enzyme BlsE. The original assignment of BlsE as a radical-mediated, redox-neutral decarboxylase is unusual because this reaction appears to serve no biosynthetic purpose and would need to be reversed by a subsequent carboxylation step. Furthermore, with the exception of BlsE, all other radical SAM decarboxylases reported to date are oxidative in nature. Careful analysis of the BlsE reaction, however, demonstrates that BlsE is not a decarboxylase but instead a lyase that catalyzes the dehydration of cytosylglucuronic acid (CGA) to form cytosyl-4′-keto-3′-deoxy-d-glucuronic acid, which can rapidly decarboxylate nonenzymatically in vitro. Analysis of substrate isotopologs, fluorinated analogues, as well as computational models based on X-ray crystal structures of the BlsE·SAM (2.09 ?) and BlsE·SAM·CGA (2.62 ?) complexes suggests that BlsE catalysis likely proceeds via direct elimination of water from the CGA C4′ α-hydroxyalkyl radical as opposed to 1,2-migration of the C3′-hydroxyl prior to dehydration. Biosynthetic and mechanistic implications of the revised assignment of BlsE are discussed.
HygY Is a Twitch Radical SAM Epimerase with Latent Dehydrogenase Activity Revealed upon Mutation of a Single Cysteine Residue
Besandre, Ronald A.,Chen, Zhang,Davis, Ian,Liu, Aimin,Liu, Hung-Wen,Ruszczycky, Mark Walter,Zhang, Jiawei
supporting information, p. 15152 - 15158 (2021/09/29)
HygY is a SPASM/twitch radical SAM enzyme hypothesized to catalyze the C2′-epimerization of galacamine during the biosynthesis of hygromycin B. This activity is confirmed via biochemical and structural analysis of the derivatized reaction products using chemically synthesized deuterated substrate, high-resolution mass spectrometry and1H NMR. Electron paramagnetic resonance spectroscopy of the reduced enzyme is consistent with ligation of two [Fe4S4] clusters characteristic of the twitch radical SAM subgroup. HygY catalyzed epimerization proceeds with incorporation of a single solvent Hydron into the talamine product facilitated by the catalytic cysteine-183 residue. Mutation of this cysteine to alanine converts HygY from a C2′-epimerase to an C2′-dehydrogenase with comparable activity. The SPASM/twitch radical SAM enzymes often serve as anaerobic oxidases making the redox-neutral epimerases in this class rather interesting. The discovery of latent dehydrogenase activity in a twitch epimerase may therefore offer new insights into the mechanistic features that distinguish oxidative versus redox-neutral SPASM/twitch enzymes and lead to the evolution of new enzyme activities.