AI Article Synopsis
- Williams-Beuren syndrome results from a deletion in chromosome region 7q11.23, leading to the loss of 26 genes, including WBSCR27, whose function was previously unknown.
- Research using NMR revealed the structure of murine WBSCR27 and categorized it as a Class I methyltransferase, showing that it binds S-(5'-adenosyl)-l-homocysteine (SAH) more tightly than its other cofactor, S-(5'-adenosyl)-l-methionine (SAM).
- WBSCR27 also exhibits nucleosidase activity, cleaving adenine from SAH and related molecules, indicating that cofactor binding influences the enzyme's structure and
Article Abstract
Williams-Beuren syndrome, characterized by numerous physiological and mental problems, is caused by the heterozygous deletion of chromosome region 7q11.23, which results in the disappearance of 26 protein-coding genes. Protein WBSCR27 is a product of one of these genes whose biological function has not yet been established and for which structural information has been absent until now. Using NMR, we investigated the structural and functional properties of murine WBSCR27. For protein in the apo form and in a complex with S-(5'-adenosyl)-l-homocysteine (SAH), a complete NMR resonance assignment has been obtained and the secondary structure has been determined. This information allows us to attribute WBSCR27 to Class I methyltransferases. The interaction of WBSCR27 with the cofactor S-(5'-adenosyl)-l-methionine (SAM) and its metabolic products - SAH, 5'-deoxy-5'-methylthioadenosine (MTA) and 5'-deoxyadenosine (5'dAdo) - was studied by NMR and isothermal titration calorimetry. SAH binds WBSCR27 much tighter than SAM, leaving open the question of cofactor turnover in the methylation reaction. One possible answer to this question is the presence of weak but detectable nucleosidase activity for WBSCR27. We found that the enzyme catalyses the cleavage of the adenine moiety from SAH, MTA and 5'dAdo, similar to the action of bacterial SAH/MTA nucleosidases. We also found that the binding of SAM or SAH causes a significant change in the structure of WBSCR27 and in the conformational mobility of the protein fragments, which can be attributed to the substrate recognition site. This indicates that the binding of the cofactor modulates the folding of the substrate-recognizing region of the enzyme.
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Article Synopsis
- Williams-Beuren syndrome (WBS) is caused by a deletion of genes on chromosome 7, leading to a variety of health issues due to protein malfunction.
- The role of the protein methyltransferase WBSCR27 in WBS remains unclear, prompting researchers to create gene knockout mouse cell lines to identify its methylation targets.
- Through structural analysis, they discovered that WBSCR27 has a characteristic Class I methyltransferase structure, and binding to S-adenosyl-L-homocysteine (SAH) helps form a substrate binding site, suggesting areas for future investigation.
Article Synopsis
- Williams-Beuren syndrome results from a deletion in chromosome region 7q11.23, leading to the loss of 26 genes, including WBSCR27, whose function was previously unknown.
- Research using NMR revealed the structure of murine WBSCR27 and categorized it as a Class I methyltransferase, showing that it binds S-(5'-adenosyl)-l-homocysteine (SAH) more tightly than its other cofactor, S-(5'-adenosyl)-l-methionine (SAM).
- WBSCR27 also exhibits nucleosidase activity, cleaving adenine from SAH and related molecules, indicating that cofactor binding influences the enzyme's structure and
NMR assignments of the WBSCR27 protein related to Williams-Beuren syndrome.
Biomol NMR Assign
October 2018
Faculty of Fundamental Medicine, Center for Magnetic Tomography and Spectroscopy, M.V. Lomonosov Moscow State University, Moscow, Russia, 119991.
Article Synopsis
- Williams-Beuren syndrome is a genetic disorder linked to a deletion of genes on chromosome 7, causing various physiological and mental health issues.
- The WBSCR27 protein, which is missing in this disorder, is suggested to be part of the SAM-dependent methyltransferase family, but its exact functions and effects of its absence are not fully understood.
- Recent research successfully assigned chemical shifts for the WBSCR27 protein in mice, revealing its secondary structure and dynamics, reinforcing its classification within class I methyltransferases.
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