Disease relevance of MOCS1

• Comparative mutational studies of MOCS1A and the small subunit of the E. coli MPT synthase (MoaD) indicate a different function of the double glycine motifs in both proteins [1].
• BACKGROUND: Molybdenum cofactor deficiency (MOCOD) is a rare, progressive neurodegenerative disorder caused by sulphite oxidase enzyme deficiency [2].

Psychiatry related information on MOCS1

• In this study, the existence of statistical relationships between intensity difference limens (IDLs) and MOCS functioning was tested in humans [3].

High impact information on MOCS1

• Mutations can be found in the majority of MoCo-deficient patients that confirm the functional role of both ORFs in the corresponding gene MOCS1 (for 'molybdenum cofactor synthesis-step 1') [4].
• Most patients harbor MOCS1 mutations, which prohibit formation of a precursor, or carry MOCS2 mutations, which abrogate precursor conversion to molybdopterin [5].
• Characterization of MOCS1A, an oxygen-sensitive iron-sulfur protein involved in human molybdenum cofactor biosynthesis [6].
• Sequence analysis of MOCS1A showed two highly conserved cysteine motifs, one near the N terminus and one near the C terminus [6].
• The human proteins MOCS1A and MOCS1B catalyze the conversion of a guanosine derivative to precursor Z during molybdenum cofactor biosynthesis [6].

Chemical compound and disease context of MOCS1

• High level expression of MOCS1A and MOCS1B in Escherichia coli resulted in the formation and accumulation of precursor Z that was subsequently converted to MPT [1].

Biological context of MOCS1

• MOCS1 and MOCS2 have a bicistronic architecture; i.e., each gene encodes two proteins in different open reading frames [7].
• The protein products, MOCS1A and B and MOCS2A and B, are expressed either from different mRNAs generated by alternative splicing or by independent translation of a bicistronic mRNA [7].
• The bicistronic MOCS1 gene has alternative start codons on two mutually exclusive exons [8].
• DAAM2 gene was linked to the MOCS1 gene on human chromosome 6p21.3 with an interval less than 1 kb [9].
• We describe here one additional kindred of Arab-Israeli origin, which is also linked to the MOCS1 locus, and demonstrate the feasibility of prenatal diagnosis and carrier detection using microsatellite markers in selected families when mutations are unknown [10].

Anatomical context of MOCS1

• To investigate the involvement of the medial olivocochlear system (MOCS) in outer hair cell (OHC) motility stabilization, evoked otoacoustic emissions (EOAEs) were recorded in 20 normal-hearing subjects and in eight vestibular-neurotomized subjects, successively in the presence and absence of low-intensity contralateral acoustic stimulation [11].
• These were: (1) middle ear dysfunction; (2) mild cochlear pathology; (3) central/medial olivocochlear efferent system (MOCS) auditory dysfunction; (4) purely psychological problems; (5) multiple auditory pathologies; (6) combined auditory dysfunction and psychological problems and (7) unknown [12].

Associations of MOCS1 with chemical compounds

• We showed that for catalytic activity MOCS1A needs an accessible C-terminal double glycine motif [1].
• 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 [13].
• We homozygously identified the CGA insertion after A666 of the MOCS1 gene which produces arginine insertion at codon 222 of MOCS1A [14].
• The results indicated that anaerobically purified MOCS1A is a monomeric protein containing two oxygen-sensitive FeS clusters, each coordinated by only three cysteine residues [6].
• MOCS1A shares homology with S-adenosylmethionine (AdoMet)-dependent radical enzymes, which catalyze the formation of protein and/or substrate radicals by reductive cleavage of AdoMet through a [4Fe-4S] cluster [6].

Other interactions of MOCS1

• Gephyrin is a protein involved in both synaptic anchoring of inhibitory ligand-gated ion channels and molybdenum cofactor synthesis [15].

Analytical, diagnostic and therapeutic context of MOCS1

• MOCS1(-/-) mice could be a suitable animal model for biochemical and/or genetic therapy approaches [16].
• These observations point to a novel form of microcompartmentalization and render the MOCS genes ideal candidates for a somatic gene therapy approach [17].
• DESIGN: Transient evoked otoacoustic emissions (TEOAE) and their suppression by the efferent activity of the medial olivocochlear system (MOCS) in response to contralateral acoustic stimulation were used to compare these processes in 18 children with SLI and 21 controls [18].

References