Catalyses the synthesis of molybdopterin from cyclic pyranopterin monophosphate. Two sulfur atoms are transferred to cyclic pyranopterin monophosphate in order to form the characteristic ene-dithiol group found in the molybdenum cofactor. Molybdopterin synthase consists of two large subunits forming a central dimer and two small subunits (molybdopterin-synthase sulfur-carrier proteins) that are thiocarboxylated at the C-terminus by EC 2.8.1.11, molybdopterin synthase sulfurtransferase. The reaction occurs in prokaryotes and eukaryotes.
Catalyses the synthesis of molybdopterin from cyclic pyranopterin monophosphate. Two sulfur atoms are transferred to cyclic pyranopterin monophosphate in order to form the characteristic ene-dithiol group found in the molybdenum cofactor. Molybdopterin synthase consists of two large subunits forming a central dimer and two small subunits (molybdopterin-synthase sulfur-carrier proteins) that are thiocarboxylated at the C-terminus by EC 2.8.1.11, molybdopterin synthase sulfurtransferase. The reaction occurs in prokaryotes and eukaryotes.
molybdenum cofactor (Moco) biosynthesis is an evolutionarily conserved pathway present in eubacteria, archaea and eukaryotes, including humans. The strong structural similarity between the small subunit of MPT synthase and ubiquitin provides evidence for the evolutionary antecedence of the Moco biosynthetic pathway to the ubiquitin dependent protein degradation pathway
characterization of mutants identified in group B patients of molybdenum cofactor deficiency, molecular mechanism leading to human molybdenum cofactor deficiency, overview
the molybdenum cofactor contains a tricyclic pyranopterin, termed molybdopterin (MPT), that bears the cis-dithiolene group responsible for molybdenum ligation. The dithiolene group of MPT is generated by MPT synthase
in the activated form of the enzyme this C-terminus is present as a thiocarboxylate. In the structure of a covalent complex of MPT synthase, an isopeptide bond is present between the C-terminus of the small subunit and a Lys side chain in the large subunit. The highly conserved active site residues are Arg39, Lys119, Lys126 and Arg140 in the large subunit
in the activated form of the enzyme this C-terminus is present as a thiocarboxylate. In the structure of a covalent complex of MPT synthase, an isopeptide bond is present between the C-terminus of the small subunit and a Lys side chain in the large subunit. The highly conserved active site residues are Arg39, Lys119, Lys126 and Arg140 in the large subunit
the crystal structure of MPT synthase reveals a heterotetrameric protein in which the C-terminus of each small subunit is inserted into a large subunit to form the active site
comparison of structures and sequences of MPT synthases from different species, overview. The side chains of the aromatic residues Phe D7, Phe D75, Tyr E55 and Trp E125 are forming the hydrophobic core of the heterodimer interface, the highly conserved active site residues are Arg39, Lys119, Lys126 and Arg140 in the large subunit
comparison of structures and sequences of MPT synthases from different species, overview. The side chains of the aromatic residues Phe D7, Phe D75, Tyr E55 and Trp E125 are forming the hydrophobic core of the heterodimer interface, the highly conserved active site residues are Arg39, Lys119, Lys126 and Arg140 in the large subunit
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
purified recombinant enzyme, vapor diffusion, protein in M NaCl, 0.1 M HEPES, pH 7.5, is mixed with mother liquor containing 20% v/v glycerol, X-ray diffraction structure determination and analysis at 1.45 A resolution
naturally occuring substitution in MOCS2B, the E168K mutation, identified in a severely affected patient, attenuates binding of precursor Z, the MPT synthase tetramer is readily formed in mixtures of MOCS2B-E168K with equimolar amounts of MOCS2A
naturally occuring substitution in MOCS2A, identified in a patient with an unusual mild form of the disease, the mutation weakens the interaction between MOCS2A and MOCS2B, the MOCS2A-V7F variant does not form a complex with MOCS2B in either its carboxylated or thiocarboxylated form, and the mutant MPT synthase shows 90% reduced activity compared to the wild-type enzyme
a deletion of Ala150 is introduced into MOCS2B, attempts to purify MOCS2B-A150DELTA fails because the protein forms inclusion bodies upon expression in the Escherichia coli cells. Construction of a MOCS2B variant lacking the first 43 amino acid residues, the DELTA1-43 variant of MOCS2B is unstable because the majority of the protein was rapidly degraded during or after purification
a deletion of Ala150 is introduced into MOCS2B, attempts to purify MOCS2B-A150DELTA fails because the protein forms inclusion bodies upon expression in the Escherichia coli cells. Construction of a MOCS2B variant lacking the first 43 amino acid residues, the DELTA1-43 variant of MOCS2B is unstable because the majority of the protein was rapidly degraded during or after purification
recombinant human subunits MOCS2A and MOCS2B from Escherichia coli strain BL21(DE3) by ammonium sulfate fractionation and gel filtration. The separately purified subunits readily assemble into a functional MPT synthase tetramer
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
DNA and amino acid sequence determination and analysis, cDNA clones ATCC 960768 from adult uterus and ATCC 331184 from fetal liver and spleen, the MOCO1 locus resides on human chromosome 5 encoding subunits MOCO1-A and MOCO1-B
MOCS2A and MOCS2B genotyping, recombinant expression of human subunits MOCS2A and MOCS2B in Escherichia coli strain BL21(DE3), functional complementation of Escherichia coli moaD and moaE mutants. In vitro translation and mutagenesis experiments of MOCS2A and MOCS2B
Mechanistic studies of human molybdopterin synthase reaction and characterization of mutants identified in group B patients of molybdenum cofactor deficiency