4fmu

Crystal structure of Methyltransferase domain of human SET domain-containing protein 2 Compound: Pr-SNF

spinqualitylabelsall models 4fmu, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4fmu is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 0UM, UNX, ZN Gene: SETD2, HIF1, HYPB, KIAA1732, KMT3A, SET2, HSPC069 (Homo sapiens) Activity: Histone-lysine N-methyltransferase, with EC number 2.1.1.43 Resources: FirstGlance, OCA, RCSB, PDBsum Function [SETD2_HUMAN] Histone methyltransferase that methylates 'Lys-36' of histone H3. H3 'Lys-36' methylation represents a specific tag for epigenetic transcriptional activation. Probably plays a role in chromatin structure modulation during elongation via its interaction with hyperphosphorylated POLR2A. Binds DNA at promoters. May also act as a transcription activator that binds to promoters. Binds to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression. Publication Abstract from PubMed Epigenetic regulations are involved in numerous physiological and pathogenic processes. Among the key regulators that orchestrate epigenetic signaling are over 50 human protein lysine methyltransferases (PKMTs). Interrogating the functions of individual PKMTs can be facilitated by target-specific PKMT inhibitors. Given the emerging need of such small molecules, we envision an approach to identify target-specific methyltransferase inhibitors by screening privileged small-molecule scaffolds against diverse methyltransferases. Here we demonstrate such feasibility by identifying the inhibitors of SETD2. N-propyl sinefungin (Pr-SNF) was shown to preferentially interact with SETD2 by matching the distinct transition-state features of SETD2's catalytically-active conformer. With Pr-SNF as a structure probe, we further revealed the dual roles of SETD2's post-SET loop on regulating substrate access through a distinct topological reconfiguration. Privileged sinefungin scaffolds are expected to have broad use as structure and chemical probes of methyltransferases. Sinefungin Derivatives as Inhibitors and Structure Probes of Protein Lysine Methyltransferase SETD2.,Zheng W, Ibanez G, Wu H, Blum G, Zeng H, Dong A, Li F, Hajian T, Allali-Hassani A, Amaya MF, Siarheyeva A, Yu W, Brown PJ, Schapira M, Vedadi M, Min J, Luo M J Am Chem Soc. 2012 Oct 8. PMID:23043551 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone methyltransferase

Proteopedia Page Contributors and Editors (what is this?)

OCA