NMR assignments of the WBSCR27 protein related to Williams-Beuren syndrome

Mariasina, Sofia S.; Petrova, Olga A.; Osterman, Ilya А.; Sergeeva, Olga V.; Ефимов, С. В.; Клочков, В. В.; Сергиев, Петр В.; Донцова, О. А.; Huang, Tai Huang; Chang, Chi‐Fon; Polshakov, Vladimir I.

doi:10.1007/s12104-018-9827-2

Cited by 3 publications

(9 citation statements)

References 19 publications

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“…One of the closest sequence homologs of WBSCR27 is a human protein WBSCR22 and its yeast ortholog Bud23 ( Mariasina et al, 2018 ). WBSCR22 is a 18S rRNA MTase involved in pre-rRNA processing and ribosome 40 S subunit biogenesis ( Haag et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…Protein samples were purified as described in Mariasina et al (2018) . Refolding was an important step in the purification procedure of the apo-form of the protein.…”

Section: Methodsmentioning

confidence: 99%

“…Refolding was an important step in the purification procedure of the apo-form of the protein. In this case after affinity chromatography on the Ni-NTA column and subsequent His-tag cleavage, the protein samples were denatured in 6 M urea, washed from endogenous SAH by dialysis, and refolded back to the native form ( Mariasina et al, 2018 ). Samples of the WBSCR27-SAH complex with identical content of the 13 C and 15 N isotopes in both protein and ligand were purified without refolding.…”

Section: Methodsmentioning

confidence: 99%

“…Earlier we reported the backbone and side chain signal assignments for the complex SAH-WBSCR27 (BMRB-27417, Mariasina et al, 2018 ) and for the apo form of the protein (BMRB-27578, Mariasina et al, 2020 ) and deposited these data in BioMagResBank ( https://bmrb.io ). This information was used to determine NMR restraints.…”

Section: Methodsmentioning

confidence: 99%

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Williams-Beuren Syndrome Related Methyltransferase WBSCR27: From Structure to Possible Function

Mariasina

Chang²,

Navalayeu³

et al. 2022

Front. Mol. Biosci.

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Williams-Beuren syndrome (WBS) is a genetic disorder associated with the hemizygous deletion of several genes in chromosome 7, encoding 26 proteins. Malfunction of these proteins induce multisystemic failure in an organism. While biological functions of most proteins are more or less established, the one of methyltransferase WBSCR27 remains elusive. To find the substrate of methylation catalyzed by WBSCR27 we constructed mouse cell lines with a Wbscr27 gene knockout and studied the obtained cells using several molecular biology and mass spectrometry techniques. We attempted to pinpoint the methylation target among the RNAs and proteins, but in all cases neither a direct substrate has been identified nor the protein partners have been detected. To reveal the nature of the putative methylation substrate we determined the solution structure and studied the conformational dynamic properties of WBSCR27 in apo state and in complex with S-adenosyl-L-homocysteine (SAH). The protein core was found to form a canonical Rossman fold common for Class I methyltransferases. N-terminus of the protein and the β6–β7 loop were disordered in apo-form, but binding of SAH induced the transition of these fragments to a well-formed substrate binding site. Analyzing the structure of this binding site allows us to suggest potential substrates of WBSCR27 methylation to be probed in further research.

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Section: Discussionmentioning

confidence: 99%

“…Protein samples were purified as described in Mariasina et al (2018) . Refolding was an important step in the purification procedure of the apo-form of the protein.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Williams-Beuren Syndrome Related Methyltransferase WBSCR27: From Structure to Possible Function

Mariasina

Chang²,

Navalayeu³

et al. 2022

Front. Mol. Biosci.

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“…Chemical shift assignment for WBSCR27 in its apo form was performed using 13 The values of the 1 Ha, 13 Ca, 13 Cb, 13 C 0 and 15 N chemical shifts were used to determine the secondary structure of the apo form of WBSCR27 and identify flexible regions of the protein backbone using TALOS+ [30]. The core of the apo-protein (a/b/a 'sandwich') is identical to that determined in the complex of WBSCR27 with SAM [8]. It contains seven bstrands alternated with six a-helices.…”

Section: Nmr Chemical Shift Assignment For Apo-wbscr27mentioning

confidence: 99%

Williams–Beuren syndrome‐related methyltransferase WBSCR27: cofactor binding and cleavage

et al. 2020

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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 0-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 0-adenosyl)-L-methionine (SAM) and its metabolic products-SAH, 5 0-deoxy-5 0-methylthioadenosine (MTA) and 5 0-deoxyadenosine (5 0 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 0 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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Organophosphorus S-adenosyl-L-methionine mimetics: synthesis, stability, and substrate properties

Rudenko,

Mariasina,

Bolikhova

et al. 2024

Front. Chem.

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S-Adenosyl-l-methionine (SAM)-mediated methylation of biomolecules controls their function and regulates numerous vital intracellular processes. Analogs of SAM with a reporter group in place of the S-methyl group are widely used to study these processes. However, many of these analogs are chemically unstable that largely limits their practical application. We have developed a new compound, SAM-PH, which contains an H-phosphinic group (-P(O)(H)OH) instead of the SAM carboxylic group. SAM-PH is significantly more stable than SAM, retains functional activity in catechol-O-methyltransferase and methyltransferase WBSCR27 reactions. The last is associated with Williams–Beuren syndrome. Rac-SAM-PH was synthesized chemically, while (R,S)-SAM-PH and its analogs were prepared enzymatically either from H-phosphinic analogs of methionine (Met-PH) or H-phosphinic analog of S-adenosyl-l-homocysteine (SAH-PH) using methionine adenosyltransferase 2A or halide methyltransferases, respectively. SAH-PH undergoes glycoside bond cleavage in the presence of methylthioadenosine nucleosidase like natural SAH. Thus, SAM-PH and its analogs are promising new tools for investigating methyltransferases and incorporating reporter groups into their substrates.

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NMR assignments of the WBSCR27 protein related to Williams-Beuren syndrome

Cited by 3 publications

References 19 publications

Williams-Beuren Syndrome Related Methyltransferase WBSCR27: From Structure to Possible Function

Williams-Beuren Syndrome Related Methyltransferase WBSCR27: From Structure to Possible Function

Williams–Beuren syndrome‐related methyltransferase WBSCR27: cofactor binding and cleavage

Organophosphorus S-adenosyl-L-methionine mimetics: synthesis, stability, and substrate properties

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