MoCo&Wco

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Rfam ID: RF01055 (MoCo (molybdenum cofactor) riboswitch)


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Timeline Description Structure&recognition References


Timeline

Start

    2007[2] Discovery of the MoCo and Wco riboswitch by the CMfinder comparative genomics pipeline

    Biochemical validation of the MoCo and Wco riboswitch 2008[3]

    2008[4] Tungsten cofactor biosynthesis pathway in E. coli

    Molybdenum cofactor biosynthesis pathway in E. coli 2013[5]

    2022[7] The MoCo riboswitch is proposed as one of promising antibacterial drug targets

    The ion-dependent folding and secondary structural features of the ligand-free MoCo riboswitch 2023[8]
2023...



Description

 The MoCo RNA motif is a conserved RNA structure that is presumed to be a riboswitch that binds molybdenum cofactor or the related tungsten cofactor. Genetic experiments support the hypothesis that the MoCo RNA motif corresponds to a genetic control element that responds to changing concentrations of molybdenum or tungsten cofactor. As these cofactors are not available in purified form, in vitro binding assays cannot be performed. However, the genetic data, complex structure of the RNA and the failure to detect a protein involved in the regulation suggest that the MoCo RNA motif corresponds to a class of riboswitches (From Wikipedia).


Gene association

Pathway for molybdenum cofactor biosynthesis in eubacteria and tungsten cofactor in Pyrococcus furiosus. Proteins in abbreviation are enzymes in the pathway except for ModABC. Proteins whose coding regions are located downstream and near the MoCo and Wco riboswitch in at least one organism are highlighted in red and blue, respectively[1,3-4].
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Gene regulation

Potential mechanism of translation regulation by the MoCo riboswitch of Escherichia coli. The ribosome binding site(RBS) is shaded red. We present the prototypical mechanism, but not all possible mechanisms[8].
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Structure and Ligand recognition

2D representation

Top: Consensus sequence and secondary structure model for the WoCo and Wco riboswitch. Bottom: Sequence of the 138 moaA RNA of Escherichia coli depicted to conform to the secondary structure model. Nucleotidesshaded in grey undergo greater rates of spontaneous 3' phosphodiester cleavage, which typically indicates an elevated level of structural flexibility relative to internucleotide linkages present in stable secondary or tertiary structures. The bar in red identifies purine nucleotides predicted to serve as a ribosome binding site and the translation start codon for moaA is boxed in green[3].

nan (Sequence from bottom structure )


Ligand recognition

Chemical structures of molybdenum cofactor (Moco) and tungsten cofactor (Tuco). The apparent KD of each cofactor is not obtained. Refer to the corresponding references for comprehensive details regarding reaction conditions and species information in measuring the dissociation constant displayed below[3].
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References

[1] Molybdenum cofactor biosynthesis and deficiency.
Schwarz, G.
Cell. Mol. Life Sci. 62, (2005).

[2] Identification of 22 candidate structured RNAs in bacteria using the CMfinder comparative genomics pipeline.
Weinberg, Z. et al.
Nucleic Acids Res. 35, (2007).

[3] A widespread riboswitch candidate that controls bacterial genes involved in molybdenum cofactor and tungsten cofactor metabolism.
Regulski, E. E. et al.
Mol. Microbiol. 68, (2008).

[4] Function of MoaB proteins in the biosynthesis of the molybdenum and tungsten cofactors.
Bevers, L. E. et al.
Biochemistry 47, (2008).

[5] Molybdenum enzymes, their maturation and molybdenum cofactor biosynthesis in Escherichia coli.
Iobbi-Nivol, C. & Leimkühler, .
Biochim. Biophys. Acta 1827, 1086–1101 (2013).

[6] Mechanism of pyranopterin ring formation in molybdenum cofactor biosynthesis.
Hover, B. M., Tonthat, N. K., Schumacher, M. A. & Yokoyama, K.
Proc. Natl. Acad. Sci. U. S. A. 112, 6347–6352 (2015).

[7] Bioinformatics and Genomic Analyses of the Suitability of Eight Riboswitches for Antibacterial Drug Targets.
Pavlova, N. & Penchovsky, R.
Antibiotics (Basel) 11, (2022).

[8] The structural features of the ligand-free moaA riboswitch and its ion-dependent folding.
Amadei, F., Reichenbach, M., Gallo, S. & Sigel, R. K. O.
J. Inorg. Biochem. 242, 112153 (2023).