Home About us Contact
|
Home About us Contact | ||
|
|
||
Molybdenum Cofactor (molybdenum + cofactor)
Selected AbstractsMaternal uniparental isodisomy is responsible for serious molybdenum cofactor deficiencyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2010HAKAN GÜMÜ Molybdenum cofactor (MoCo) deficiency is a rare autosomal recessive inherited metabolic disorder resulting in the combined deficiency of aldehyde oxidase, xanthine dehydrogenase, and sulfite oxidase. We report a male infant with MoCo deficiency whose clinical findings consisted of microcephaly, intractable seizures soon after birth, feeding difficulties, and developmental delay. Sequencing of MOCS1, MOCS2, and GEPH genes, and single nucleotide polymorphism genotyping array analysis showed, to our knowledge, unusual inheritance of MoCo deficiency/maternal uniparental isodisomy for the first time in the literature. At 10 months of age, he now has microcephaly and developmental delay, and his seizures are controlled with phenobarbital, clonozepam, and vigabatrin therapy. [source] Isolated sulfite oxidase deficiency: identification of 12 novel SUOX mutations in 10 patientsHUMAN MUTATION, Issue 1 2002Jean L. Johnson Abstract We report twelve novel mutations in patients with isolated sulfite oxidase deficiency. The mutations are in SUOX, the gene that encodes the molybdohemoprotein sulfite oxidase. These include two frameshift mutations, a four-basepair deletion (562del4) and a single-basepair insertion (113insC), both resulting in premature termination. Nonsense mutations predicting Y343X and Q364X substitutions were identified in a homozygous state in three patients, the latter in two sibs. The remaining eight are missense mutations generating single amino acid substitutions. From the position of the substituted residues, seven of these mutations are considered to be causative of the enzyme deficiency: I201L, R211Q, G305S, R309H, K322R, Q339R, and W393R. The eighth, a C>T transition, predicts an R319C substitution, which could affect the binding of the molybdenum cofactor and thus severely reduce sulfite oxidase activity. This mutation, however, is downstream of a frameshift mutation and is therefore not the causative mutation in this individual. © 2002 Wiley-Liss, Inc. [source] Molybdenum cofactor amounts in Chlamydomonas reinhardtii depend on the Nit5 gene function related to molybdate transportPLANT CELL & ENVIRONMENT, Issue 11 2000A. Llamas ABSTRACT Strain 21gr from Chlamydomonas reinhardtii is a cryptic mutant defective in the Nit5 gene related to the biosynthesis of molybdenum cofactor (MoCo). In spite of this mutation, this strain has active MoCo and can grow on nitrate media. In genetic crosses, the Nit5 mutation cosegregated with a phenotype of resistance to high concentrations of molybdate and tungstate. Molybdate/tungstate toxicity was much higher in nitrate than in ammonium media. Strain 21gr showed lower amounts of MoCo activity than the wild type both when grown in nitrate and after growth in ammonium and nitrate induction. However, nitrate reductase (NR) specific activity was similar in wild type and 21gr cells. Tungstate, either at nanomolar concentrations in nitrate media or at micromolar concentrations during growth in ammonium and nitrate induction, strongly decreased MoCo and NR amounts in wild-type cells but had a slight effect in 21gr cells. Molybdate uptake activity of ammonium-grown cells from both the wild-type and 21gr strains was small and blocked by sulphate 0·3 mM. However, cells from nitrate medium showed a molybdate uptake activity insensitive to sulphate. This uptake activity was much higher and more sensitive to inhibition by tungstate in the wild type than in strain 21gr. These results suggest that strain 21gr has a high affinity and low capacity molybdate transport system able to discriminate efficiently tungstate, and lacks a high capacity molybdate/tungstate transport system, which operates in wild-type cells upon nitrate induction. This high capacity molybdate transport system would account for both the stimulating effect of molybdate on MoCo amounts and the toxic effects of tungstate and molybdate when present at high concentrations. [source] The maize Viviparous10/Viviparous13 locus encodes the Cnx1 gene required for molybdenum cofactor biosynthesisTHE PLANT JOURNAL, Issue 2 2006Timothy G. Porch Summary Abscisic acid (ABA), auxin and nitrate are important signaling molecules that affect plant growth responses to the environment. The synthesis or metabolism of these compounds depends on the molybdenum cofactor (MoCo). We show that maize (Zea mays) viviparous10 (vp10) mutants have strong precocious germination and seedling lethal phenotypes that cannot be rescued with tissue culture. We devised a novel PCR-based method to clone a transposon-tagged allele of vp10, and show that Vp10 encodes the ortholog of Cnx1, which catalyzes the final common step of MoCo synthesis. The seedling phenotype of vp10 mutants is consistent with disruptions in ABA and auxin biosynthesis, as well as a disruption in nitrate metabolism. Levels of ABA and auxin are reduced in vp10 mutants, and vp10 seedlings lack MoCo-dependent enzyme activities that are repairable with exogenous molybdenum. vp10 and an Arabidopsis cnx1 mutant, chlorate6 (chl6), have similar defects in aldehyde oxidase (AO) enzyme activity, which is required for ABA synthesis. Surprisingly, chl6 mutants do not show defects in abiotic stress responses. These observations confirm an orthologous function for Cnx1 and Vp10, as well as defining a characteristic viviparous phenotype to identify other maize cnx mutants. Finally, the vp10 mutant phenotype suggests that cnx mutants can have auxin- as well as ABA-biosynthesis defects, while the chl6 mutant phenotype suggests that low levels of AO activity are sufficient for normal abiotic stress responses. [source] The maize viviparous15 locus encodes the molybdopterin synthase small subunitTHE PLANT JOURNAL, Issue 2 2006Masaharu Suzuki Summary A new Zea mays viviparous seed mutant, viviparous15 (vp15), was isolated from the UniformMu transposon-tagging population. In addition to precocious germination, vp15 has an early seedling lethal phenotype. Biochemical analysis showed reduced activities of several enzymes that require molybdenum cofactor (MoCo) in vp15 mutant seedlings. Because MoCo is required for abscisic acid (ABA) biosynthesis, the viviparous phenotype is probably caused by ABA deficiency. We cloned the vp15 mutant using a novel high-throughput strategy for analysis of high-copy Mu lines: We used MuTAIL PCR to extract genomic sequences flanking the Mu transposons in the vp15 line. The Mu insertions specific to the vp15 line were identified by in silico subtraction using a database of MuTAIL sequences from 90 UniformMu lines. Annotation of the vp15 -specific sequences revealed a Mu insertion in a gene homologous to human MOCS2A, the small subunit of molybdopterin (MPT) synthase. Molecular analysis of two allelic mutations confirmed that Vp15 encodes a plant MPT synthase small subunit (ZmCNX7). Our results, and a related paper reporting the cloning of maize viviparous10, demonstrate robust cloning strategies based on MuTAIL-PCR. The Vp15/CNX7, together with other CNX genes, is expressed in both embryo and endosperm during seed maturation. Expression of Vp15 appears to be regulated independently of MoCo biosynthesis. Comparisons of Vp15 loci in genomes of three cereals and Arabidopsis thaliana identified a conserved sequence element in the 5, untranslated region as well as a micro-synteny among the cereals. [source] Structures of apo and GTP-bound molybdenum cofactor biosynthesis protein MoaC from Thermus thermophilus HB8ACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2010Shankar Prasad Kanaujia The first step in the molybdenum cofactor (Moco) biosynthesis pathway involves the conversion of guanosine triphosphate (GTP) to precursor Z by two proteins (MoaA and MoaC). MoaA belongs to the S -adenosylmethionine-dependent radical enzyme superfamily and is believed to generate protein and/or substrate radicals by reductive cleavage of S -adenosylmethionine using an Fe,S cluster. MoaC has been suggested to catalyze the release of pyrophosphate and the formation of the cyclic phosphate of precursor Z. However, structural evidence showing the binding of a substrate-like molecule to MoaC is not available. Here, apo and GTP-bound crystal structures of MoaC from Thermus thermophilus HB8 are reported. Furthermore, isothermal titration calorimetry experiments have been carried out in order to obtain thermodynamic parameters for the protein,ligand interactions. In addition, molecular-dynamics (MD) simulations have been carried out on the protein,ligand complex of known structure and on models of relevant complexes for which X-ray structures are not available. The biophysical, structural and MD results reveal the residues that are involved in substrate binding and help in speculating upon a possible mechanism. [source] Cell biology of molybdenumBIOFACTORS, Issue 5 2009Ralf R. Mendel Abstract The transition element molybdenum (Mo) is an essential micronutrient that is needed as catalytically active metal during enzyme catalysis. In humans four enzymes depend on Mo: sulfite oxidase, xanthine oxidoreductase, aldehyde oxidase, and mitochondrial amidoxime reductase. In addition to these enzymes, plants harbor a fifth Mo-enzyme namely nitrate reductase. To gain biological activity and fulfill its function in enzymes, Mo has to be complexed by a pterin compound thus forming the molybdenum cofactor. This article will review the way that Mo takes from uptake into the cell, via formation of the molybdenum cofactor and its storage, up to the final insertion of the molybdenum cofactor into apometalloenzymes. © 2009 International Union of Biochemistry and Molecular Biology, Inc. [source] | ||||||||||