Molybdopterin synthase

complexed with molybdenum to form molybdenum cofactor (MoCo). MPT synthase catalyses the following chemical reaction

heterodimeric and coded for by the MOCS2 gene.^[3] Genetic deficiencies of enzymes such as MPT synthase, which are involved in MoCo biosynthesis, lead to MoCo deficiency, a rare disease that results in severe neurological abnormalities.^[4][5][6][7]

dimer.^[1][4][5] The C-terminus of each small subunit is inserted into a large subunit to form the active site.^[4] In the enzyme's activated form the C-terminus is present as a thiocarboxylate, which acts as the sulfur donor to precursor Z in MoCo biosynthesis.^[4] As a result, the active site of the enzyme must be in close proximity to the C-terminus of the small subunit (i.e. MoaD in prokaryotes). The high resolution crystal structure of the enzyme also reveals the presence of a binding pocket for the terminal phosphate of molybdopterin and suggests a possible binding site for the pterin moiety present both in precursor Z and molybdopterin.^[8]

common ancestor with ubiquitin.^[9]

sulfhydryl groups.^[10] E-coli MPT synthase is activated by the formation of a thiocarboxylate group at the second glycine of its C-terminal Gly-Gly motif, which serves as the sulfur donor for the formation of the diothiolene group in MPT.^[5][11] That is, the mechanism on MPT synthase depends on the interconversion between the activated form of MoaD with the thiocarboxylate group and the MoaE protein^[8] In the final step of MoCo biosynthesis, molybendum is incorporated to MPT by the two-domain protein gephyrin.^[5][6] MPT synthase sulfurylase recharges MPT synthase with a sulfur atom after each catalytic cycle.^[9]

redox reaction.^[4]

Genetic defects in MoCo biosynthesis lead to MoCo deficiency.^[4] These genetic defects affect the formation of precursor Z (known as group A MoCo deficiency) or the conversion of precursor Z to MoCo by MPT synthase (known as group B MoCo deficiency).^[7][12] MOCS1 is defective for group A (the majority of patients), and encodes two enzymes involved in the formation of precursor Z.^[7][12] MOCS2 is defective for group B and encodes the small and large subunits of MPT synthase.^[7][12] Groups A and B of deficiency show an identical phenotype, characterized by neonatal seizures, attenuated brain growth, dislocated ocular lenses, feeding difficulties, among other neurological symptoms.^{[4][5][6][7][12]} This rare but severe deficiency is an autosomal recessive trait, which usually results in early childhood death as there is currently no available treatment.^[4][5][6][7]