Conformational flexibility influences structure–function relationships in tyrosyl protein sulfotransferase-2

Singh, Warispreet, Karabencheva-Christova, Tatyana, Black, Gary, Sparagano, Olivier and Christov, Christo (2016) Conformational flexibility influences structure–function relationships in tyrosyl protein sulfotransferase-2. RSC Advances, 6 (14). pp. 11344-11352. ISSN 2046-2069

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Tyrosine sulfation is a very important posttranslational modification of proteins. It is catalyzed by tyrosylprotein sulfotransferase and recently became increasingly important for biomedicine and pharmacy. An important insight about structure–activity relationships of human tyrosylprotein sulfotransferase has been received by elucidating the crystal structure, but there is still no understanding about how conformational flexibility and dynamics which are fundamental protein properties influence structure–function relationships of the enzyme. In order to provide this missing but crucially important knowledge we performed a comprehensive atomistic molecular dynamics study which revealed that (i) the conformational flexibility influences sensitively key structural determinants and interactions between the enzyme, the substrate and the cofactor; (ii) a more open conformation adopted by the substrate for binding in TPST 2; (iii) the mutations of key residues related with catalysis and binding change alter the enzyme structure and influence important interactions between the enzyme, the cofactor and the substrate.

Item Type: Article
Subjects: F100 Chemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Becky Skoyles
Date Deposited: 17 Feb 2016 11:55
Last Modified: 31 Jul 2021 17:45

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