Класифікація конформацій сайтів зв’язування тирозинфосфатази 1B

• Видавець: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
• Дата: 2024
• Автори: Tanchuk, Vsevolod Y., Kobzar, Olexandr L., Vovk, Andriy I.
• Формат: Стаття
• Опубліковано: V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2024
• Теми: PTP1B; binding sites; conformations; clustering; structure similarity
• Онлайн доступ: https://bioorganica.com.ua/index.php/journal/article/view/84

Our previous work on classification of binding site conformations of protein tyrosine phosphatase 1B was published in 2012. It was found that 102 active sites from 91 PDB files can be divided into 5 major clusters. The number of structures in the RSCB Protein data bank has almost tripled since that time, and the number of PTP1B structures has more than quadrupled. It emphasizes the importance of this enzyme. In the present paper, 793 sites from 374 pdb files available now were analyzed and clustered. The clusters were found to be very similar, though the number of structures increased in all of them. In general, the situation has not substantially changed since the first investigation. Clusters with closed WPD loop even retained their centroids. Most new conformations appear in one open-loop cluster, where ligands interact with the area close to Cys215 in the catalytic center, or some distant from the WPD loop amino acid residues like Ser55. The updated clusters can be used for designing inhibitors of PTP1B