Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Mechanistic studies of human molybdopterin synthase reaction and characterization of mutants identified in group B patients of molybdenum cofactor deficiency.
-
Purified human MOCS2A and MOCS2B assemble into a functional MPT synthase tetramer; the sulfur for the MPT dithiolene group is carried as a C-terminal thiocarboxylate on the small subunit MOCS2A.
"MOCS2A and MOCS2B were purified after heterologous expression in E. coli, and the separately purified subunits readily assemble into a functional MPT synthase tetramer."
Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans.
-
In a defined in vitro system, sulfurated MOCS3 provides the sulfur for thiocarboxylation of MOCS2A, enabling MPT synthesis; the MPT synthase subunits are cytosolic.
"the sulfurated form of MOCS3-RLD was able to provide the sulfur for the thiocarboxylation of MOCS2A, the small MPT synthase subunit in humans."
Ten novel mutations in the molybdenum cofactor genes MOCS1 and MOCS2 and in vitro characterization of a MOCS2 mutation that abolishes the binding ability of molybdopterin synthase.
-
A disease-causing MOCS2B variant abolishes binding of both precursor Z and the small subunit MOCS2A, defining MOCS2B's role in complex assembly and substrate binding.
"The mutation was expressed in vitro and was found to abolish the binding affinities of the large subunit of molybdopterin synthase (MOCS2B) for both precursor Z and the small subunit of molybdopterin synthase (MOCS2A)."
Investigation of molybdenum cofactor deficiency due to MOCS2 deficiency in a newborn baby.
-
Human recombinant WT MOCS2B binds MOCS2A (Kd = 0.36 uM) and supports MPT synthesis, whereas the MOCODB1 variant S140F disrupts complex assembly and abolishes activity.
"While WT MOCS2B showed an effective MPT synthesis (determined by the oxidation product FormA, Fig. 2E), MOCS2B-S140F was only able to produce low levels of MPT at high concentrations of MOCS2A."
Moco biosynthesis and the ATAC acetyltransferase engage translation initiation by inhibiting latent PKR activity.
-
Human MPT synthase together with the ATAC complex directly binds and inhibits the stress kinase PKR, suppressing JNK and eIF2-alpha phosphorylation to promote translation initiation - a moonlighting role of MPT synthase.
"MPT synthase and ATAC directly interacted with PKR and suppressed latent autophosphorylation of PKR and its downstream phosphorylation of JNK and eukaryotic initiation factor 2α (eIF2α)."
Sulfhydrylation and ring cleavage of precursor Z
Molybdenum cofactor biosynthesis