| Identification and characterization of the first mutation (Arg776Cys) in the C-terminal domain of the Human Molybdenum Cofactor Sulfurase (HMCS) associated with type II classical xanthinuria. | |
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MedLine Citation:
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PMID: 17368066 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Classical xanthinuria type II is an autosomal recessive disorder characterized by deficiency of xanthine dehydrogenase and aldehyde oxidase activities due to lack of a common sulfido-olybdenum cofactor (MoCo). Two mutations, both in the N-terminal domain of the Human Molybdenum Cofactor Sulfurase (HMCS), were reported in patients with type II xanthinuria. Whereas the N-terminal domain of HMCS was demonstrated to have cysteine desulfurase activity, the C-terminal domain hypothetically transfers the sulfur to the MoCo. We describe the first mutation in the C-terminal domain of HMCS identified in a Bedouin-Arab child presenting with urolithiasis and in an asymptomatic Jewish female. Patients were diagnosed with type II xanthinuria by homozygosity mapping and/or allopurinol loading test. The Bedouin-Arab child was homozygous for a c.2326C>T (p.Arg776Cys) mutation, while the female patient was compound heterozygous for this and a novel c.1034insA (p.Gln347fsStop379) mutation in the N-terminal domain of HMCS. Cosegregation of the homozygous mutant genotype with hypouricemia and hypouricosuria was demonstrated in the Bedouin family. Haplotype analysis indicated that p.Arg776Cys is a recurrent mutation. Arg776 together with six surrounding amino acid residues were found fully conserved and predicted to be buried in homologous eukaryotic MoCo sulfurases. Moreover, Arg776 is conserved in a diversity of eukaryotic and prokaryotic proteins that posses a domain homologous to the C-terminal domain of HMCS. Our findings suggest that Arg776 is essential for a core structure of the C-terminal domain of the HMCS and identification of a mutation at this site may contribute clarifying the mechanism of MoCo sulfuration. |
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Authors:
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Hava Peretz; Meirav Shtauber Naamati; David Levartovsky; Ayala Lagziel; Esther Shani; Ivona Horn; Hanna Shalev; Daniel Landau |
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Publication Detail:
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Type: Journal Article Date: 2007-03-23 |
Journal Detail:
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Title: Molecular genetics and metabolism Volume: 91 ISSN: 1096-7192 ISO Abbreviation: Mol. Genet. Metab. Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-04-13 Completed Date: 2007-07-25 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9805456 Medline TA: Mol Genet Metab Country: United States |
Other Details:
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Languages: eng Pagination: 23-9 Citation Subset: IM |
Affiliation:
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Clinical Biochemistry Laboratory, Sourasky Medical Center, Tel Aviv, Israel. hperetz@tasmc.health.gov.il |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aldehyde Oxidase
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deficiency*,
genetics,
metabolism Allopurinol / metabolism Amino Acid Sequence Amino Acid Substitution* Arginine / genetics Base Sequence Coenzymes / metabolism Cysteine / genetics Female Homozygote Humans Infant, Newborn Male Metalloproteins / metabolism Mutation Pedigree Phylogeny Protein Structure, Tertiary Pteridines / metabolism Sequence Alignment Sulfurtransferases / chemistry, genetics*, metabolism Xanthine Dehydrogenase / deficiency*, genetics, metabolism Xanthines / blood, urine* |
| Chemical | |
Reg. No./Substance:
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0/Coenzymes; 0/Metalloproteins; 0/Pteridines; 0/Xanthines; 315-30-0/Allopurinol; 52-90-4/Cysteine; 73508-07-3/molybdenum cofactor; 74-79-3/Arginine; EC 1.17.1.4/Xanthine Dehydrogenase; EC 1.2.3.1/Aldehyde Oxidase; EC 2.8.1.-/MOCOS protein, human; EC 2.8.1.-/Sulfurtransferases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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