Molybdenum cofactor biosynthesis, MoeB <p>The majority of molybdenum-containing enzymes utilise a molybdenum cofactor (MoCF or Moco) consisting of a Mo atom coordinated via a cis-dithiolene moiety to molybdopterin (MPT). MoCF is ubiquitous in nature, and the pathway for MoCF biosynthesis is conserved in all three domains of life. MoCF-containing enzymes function as oxidoreductases in carbon, nitrogen, and sulphur metabolism [<cite idref="PUB00034759"/>, <cite idref="PUB00034757"/>]. </p> <p>In <taxon tax_id="562">Escherichia coli</taxon>, biosynthesis of MoCF is a three stage process. It begins with the MoaA and MoaC conversion of GTP to the meta-stable pterin intermediate precursor Z. The second stage involves MPT synthase (MoaD and MoaE), which converts precursor Z to MPT; MoeB is involved in the recycling of MPT synthase. The final step in MoCF synthesis is the attachment of mononuclear Mo to MPT, a process that requires MoeA and which is enhanced by MogA in an Mg2 ATP-dependent manner [<cite idref="PUB00034758"/>]. MoCF is the active co-factor in eukaryotic and some prokaryotic molybdo-enzymes, but the majority of bacterial enzymes requiring MoCF, need a modification of MTP for it to be active; MobA is involved in the attachment of a nucleotide monophosphate to MPT resulting in the MGD co-factor, the active co-factor for most prokaryotic molybdo-enzymes. Bacterial two-hybrid studies have revealed the close interactions between MoeA, MogA, and MobA in the synthesis of MoCF [<cite idref="PUB00015635"/>]. Moreover the close functional association of MoeA and MogA in the synthesis of MoCF is supported by fact that the known eukaryotic homologues to MoeA and MogA exist as fusion proteins: CNX1 (<db_xref db="SWISSPROT" dbkey="Q39054"/>) of <taxon tax_id="3702">Arabidopsis thaliana</taxon> (Mouse-ear cress), mammalian Gephryin (e.g. <db_xref db="SWISSPROT" dbkey="Q9NQX3"/>) and <taxon tax_id="7227">Drosophila melanogaster</taxon> (Fruit fly) Cinnamon (<db_xref db="SWISSPROT" dbkey="P39205"/>) [<cite idref="PUB00015921"/>].</p><p> The <taxon tax_id="562">Escherichia coli</taxon> protein is involved in molybdenum cofactor (MoCF) biosynthesis, an evolutionarily conserved pathway. MoeB activates the C terminus of MoaD to form an acyl-adenylate, which is subsequently converted to a thiocarboxylate that acts as the sulphur donor during Moco biosynthesis. The structure of MoeB consists of a three-layer sandwich of alpha/beta/alpha [<cite idref="PUB00011756"/>]. The sandwich is composed of eight beta-strands, which form a continuous mixed beta sheet in the order 32145678 surrounded by eight helices. Beta strands 6 and 8 are antiparallel to the rest. The N-terminal half of the sheet contains the ATP nucleotide-binding site, which is similar to that of the NAD-binding Rossmann fold. A loop between beta-1 and alpha-3 contains a glycine-rich motif similar to the P loop found in enzymes that hydrolyse ATP. The C-terminal half of the sheet contains a fold that is similar to that found in a family of sugar-binding proteins. </p>