Structure of the molybdenum cofactor genes in <i>Drosophila</i>

Kamdar, Kim P; Primus, J. P.; Shelton, M.; Archangeli, L. L.; Wittle, A E; Finnerty, Victoria

doi:10.1042/bst0250778

Cited by 16 publications

(12 citation statements)

References 16 publications

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“…At least six gene products involved in Mocobiosynthesis have been identified in Escherichia coli (7), plants (8), and humans (9). For the E. coli proteins MogA and MoeA and their putative homologs-cinnamon in Drososphila melanogaster (10) and Cnx1 in Arabidopsis thaliana (11)-a function in the transfer and͞or activation of molybdate for incorporation into MPT has been suggested (8,11,12). The demonstration of high-affinity binding of MPT to Cnx1 is consistent with this idea (13).…”

supporting

confidence: 62%

The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells

Stallmeyer

Schwarz²,

Schulze³

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

140

116

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The molybdenum cofactor (Moco), a highly conserved pterin compound complexing molybdenum, is required for the enzymatic activities of all molybdenum enzymes except nitrogenase. Moco is synthesized by a unique and evolutionarily old pathway that requires the activities of at least six gene products. Some of the proteins involved in bacterial, plant, and invertebrate Moco biosynthesis show striking homologies to the primary structure of gephyrin, a polypeptide required for the clustering of inhibitory glycine receptors in postsynaptic membranes in the rat central nervous system. Here, we show that gephyrin binds with high affinity to molybdopterin, the metabolic precursor of Moco. Furthermore, gephyrin expression can reconstitute Moco biosynthesis in Moco-deficient bacteria, a molybdenum-dependent mouse cell line, and a Moco-deficient plant mutant. Conversely, inhibition of gephyrin expression by antisense RNA expression in cultured murine cells reduces their Moco content significantly. These data indicate that in addition to clustering glycine receptors, gephyrin also is involved in Moco biosynthesis and illustrate the remarkable conservation of its function in Moco biosynthesis throughout phylogeny.

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supporting

confidence: 62%

The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells

Stallmeyer

Schwarz²,

Schulze³

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

140

116

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“…Homology lies within the N-and C-terminal domains of gephyrin, which are separated by an intervening region of ϳ170 amino acids that harbors multiple protein interaction domains (17). Similar multi-domain proteins comprising both MogA and MoeA homologous domains are found in Drosophila melanogaster (cinnamon) (18) and Arabidopsis thaliana (Cnx1) (19), in which they have also been shown to be implicated in Moco biosynthesis.…”

mentioning

confidence: 99%

X-ray Crystal Structure of the Trimeric N-terminal Domain of Gephyrin

Solà

Kneussel

Heck³

et al. 2001

Journal of Biological Chemistry

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Gephyrin is a ubiquitously expressed protein that, in the central nervous system, forms a submembraneous scaffold for anchoring inhibitory neurotransmitter receptors in the postsynaptic membrane. The N-and Cterminal domains of gephyrin are homologous to the Escherichia coli enzymes MogA and MoeA, respectively, both of which are involved in molybdenum cofactor biosynthesis. This enzymatic pathway is highly conserved from bacteria to mammals, as underlined by the ability of gephyrin to rescue molybdenum cofactor deficiencies in different organisms. Here we report the x-ray crystal structure of the N-terminal domain (amino acids 2-188) of rat gephyrin at 1.9-Å resolution. Gephyrin-(2-188) forms trimers in solution, and a sequence motif thought to be involved in molybdopterin binding is highly conserved between gephyrin and the E. coli protein. The atomic structure of gephyrin-(2-188) resembles MogA, albeit with two major differences. The path of the Cterminal ends of gephyrin-(2-188) indicates that the central and C-terminal domains, absent in this structure, should follow a similar 3-fold arrangement as the Nterminal region. In addition, a central ␤-hairpin loop found in MogA is lacking in gephyrin-(2-188). Despite these differences, both structures show a high degree of surface charge conservation, which is consistent with their common catalytic function.

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“…First, in Synechococcus sp., the MoaC ortholog is fused to the homolog of either MoaB or MogA (41). Second, MogA and MoeA are combined to form the multifunctional protein gephyrin in mammals (13), Cnx1 in plants (15), and cinnamon in insects (14). All of the protein-protein complexes observed in vivo (40, except for MobB-MobA, contain either MogA or MoeA, the structural homologs of MoaB.…”

Section: Discussionmentioning

confidence: 99%

“…The twisted ␤ sheet with a ␤ 2 1␤ 1 1␤ 3 1␤ 6 1␤ 5 2␤ 4 1 topology is formed by five parallel ␤ strands, ␤ 2 (residues 43-50), ␤ 1 (12)(13)(14)(15)(16)(17)(18), ␤ 3 (72-76), ␤ 6 (131-136), ␤ 4 (97-98), and one antiparallel ␤ 5 (124 -128) inserted between ␤ 6 and a very short ␤ 4 . The ␤ sheet is sandwiched between four ␣ helices, a 1 (residues 23-40) and ␣ 5 (139 -150) on one side and ␣ 2 (53-67) and ␣ 3 (86 -92) on the other.…”

Section: Table I Basic Data Collection and Processing Statistics For mentioning

confidence: 99%

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The Crystal Structure of Escherichia coli MoaB Suggests a Probable Role in Molybdenum Cofactor Synthesis

Sanishvili

Beasley

Skarina

et al. 2004

Journal of Biological Chemistry

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The crystal structure of Escherichia coli MoaB was determined by multiwavelength anomalous diffraction phasing and refined at 1.6-Å resolution. The molecule displayed a modified Rossman fold. MoaB is assembled into a hexamer composed of two trimers. The monomers have high structural similarity with two proteins, MogA and MoeA, from the molybdenum cofactor synthesis pathway in E. coli, as well as with domains of mammalian gephyrin and plant Cnx1, which are also involved in molybdopterin synthesis. Structural comparison between these proteins and the amino acid conservation patterns revealed a putative active site in MoaB. The structural analysis of this site allowed to advance several hypothesis that can be tested in further studies.

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Structure of the molybdenum cofactor genes in Drosophila

Cited by 16 publications

References 16 publications

The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells

The neurotransmitter receptor-anchoring protein gephyrin reconstitutes molybdenum cofactor biosynthesis in bacteria, plants, and mammalian cells

X-ray Crystal Structure of the Trimeric N-terminal Domain of Gephyrin

The Crystal Structure of Escherichia coli MoaB Suggests a Probable Role in Molybdenum Cofactor Synthesis

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