5EMJ

Crystal structure of PRMT5:MEP50 with Compound 8 and sinefungin

Summary for 5EMJ

• Entry DOI: 10.2210/pdb5emj/pdb
• Related: 5EMK 5EML 5EMM
• Descriptor: Protein arginine N-methyltransferase 5, Methylosome protein 50, SINEFUNGIN, ... (6 entities in total)
• Functional Keywords: protein-inhibitor complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : O14744; Nucleus: Q9BQA1
• Total number of polymer chains: 2
• Total formula weight: 112789.31

Authors

Boriack-Sjodin, P.A.,Jin, L. (deposition date: 2015-11-06, release date: 2016-02-24, Last modification date: 2024-10-23)

Primary citation

Duncan, K.W.,Rioux, N.,Boriack-Sjodin, P.A.,Munchhof, M.J.,Reiter, L.A.,Majer, C.R.,Jin, L.,Johnston, L.D.,Chan-Penebre, E.,Kuplast, K.G.,Porter Scott, M.,Pollock, R.M.,Waters, N.J.,Smith, J.J.,Moyer, M.P.,Copeland, R.A.,Chesworth, R.
Structure and Property Guided Design in the Identification of PRMT5 Tool Compound EPZ015666.
ACS Med Chem Lett, 7:162-166, 2016

PubMed Abstract: The recent publication of a potent and selective inhibitor of protein methyltransferase 5 (PRMT5) provides the scientific community with in vivo-active tool compound EPZ015666 (GSK3235025) to probe the underlying pharmacology of this key enzyme. Herein, we report the design and optimization strategies employed on an initial hit compound with poor in vitro clearance to yield in vivo tool compound EPZ015666 and an additional potent in vitro tool molecule EPZ015866 (GSK3203591).

PubMed: 26985292
DOI: 10.1021/acsmedchemlett.5b00380

Experimental method

X-RAY DIFFRACTION (2.273 Å)