Proof-of-Concept Method to Study Uncharacterized Methyltransferases Using PRDM15

• Published in: International journal of molecular sciences Vol. 24; no. 2; p. 1327
• Main Authors: Zhao, Li-Na, Guccione, Ernesto, Kaldis, Philipp
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.01.2023; MDPI
• Subjects: Blood cancer; Computer applications; CRISPR; Deregulation; DNA methylation; DNA-Binding Proteins - metabolism; Enzymatic activity; Gene expression; Histone-Lysine N-Methyltransferase - metabolism; Histones; Histones - genetics; Histones - metabolism; Humans; Kinases; Lymphoma; Medical and Health Sciences; Medical Biotechnology; Medical prognosis; Medicin och hälsovetenskap; Medicinsk bioteknologi; methyl transfer; Methylation; Methyltransferase; Methyltransferases - metabolism; Neoplasms; Peptides; PRDM15; PRDM15 gene effect; PRDM15 substrates; Proteins; Reaction mechanisms; Transcription Factors - genetics; Transcription Factors - metabolism; Tumors; PRDM15; methyltransferase; PRDM15 gene effect; PRDM15 substrates; methyl transfer
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24021327

The PRDM family of methyltransferases has been implicated in cellular proliferation and differentiation and is deregulated in human diseases, most notably in cancer. PRDMs are related to the SET domain family of methyltransferases; however, from the 19 PRDMs only a few PRDMs with defined enzymatic activities are known. PRDM15 is an uncharacterized transcriptional regulator, with significant structural disorder and lack of defined small-molecule binding pockets. Many aspects of PRDM15 are yet unknown, including its structure, substrates, reaction mechanism, and its methylation profile. Here, we employ a series of computational approaches for an exploratory investigation of its potential substrates and reaction mechanism. Using the knowledge of PRDM9 and current knowledge of PRDM15 as basis, we tried to identify genuine substrates of PRDM15. We start from histone-based peptides and learn that the native substrates of PRDM15 may be non-histone proteins. In the future, a combination of sequence-based approaches and signature motif analysis may provide new leads. In summary, our results provide new information about the uncharacterized methyltransferase, PRDM15.