{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:08:31Z","timestamp":1770293311292,"version":"3.49.0"},"reference-count":57,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T00:00:00Z","timestamp":1729987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["MIS5002550"],"award-info":[{"award-number":["MIS5002550"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>SR\/RS dipeptide repeats vary in both length and position, and are phosphorylated by SR protein kinases (SRPKs). PIM\u20101L, the long isoform of PIM\u20101 kinase, the splicing of which has been implicated in acute myeloid leukemia, contains a domain that consists largely of repeating SR\/RS and SH\/HS dipeptides (SR\/SH\u2010rich). In order to extend our knowledge on the specificity and cellular functions of SRPK1, here we investigate whether PIM\u20101L could act as substrate of SRPK1 by a combination of biochemical and computational approaches. Our biochemical data showed that the SR\/SH\u2010rich domain of PIM\u20101L was able to associate with SRPK1, yet it could not act as a substrate but, instead, inactivated the kinase. In line with our biochemical data, molecular modeling followed by a microsecond\u2010scale all\u2010atom molecular dynamics (MD) simulation suggests that the SR\/SH\u2010rich domain acts as a pseudo\u2010docking peptide that binds to the same acidic docking\u2010groove used in other SRPK1 interactions and induces inactive SRPK1 conformations. Comparative community network analysis of the MD trajectories, unraveled the dynamic architecture of apo SRPK1 and notable alterations of allosteric communications upon PIM\u20101L peptide binding. This analysis also allowed us to identify key SRPK1 residues, including unique ones, with a pivotal role in mediating allosteric signal propagation within the kinase core. Interestingly, most of the identified amino acids correspond to cancer\u2010associated amino acid changes, validating our results. In total, this work provides insights not only on the details of SRPK1 inhibition by the PIM\u20101L SR\/SH\u2010domain, but also contributes to an in\u2010depth understanding of SRPK1 regulation.<\/jats:p>","DOI":"10.1002\/prot.26757","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T04:59:05Z","timestamp":1730091545000},"page":"629-653","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["<scp>PIM<\/scp>\u2010<scp>1L<\/scp> Kinase Binds to and Inactivates <scp>SRPK1<\/scp>: A Biochemical and Molecular Dynamics Study"],"prefix":"10.1002","volume":"93","author":[{"given":"Nastazia","family":"Lesgidou","sequence":"first","affiliation":[{"name":"Institute of Biosciences and Applications National Center for Scientific Research \u201cDemokritos\u201d  Athens 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