Sandbox Reserved 897

This Sandbox is Reserved from Jan 13 through July 31, 2020 for use in the course Protein Structure in Drug Discovery taught by Karen C. Glass at the ACPHS, Colchester, United States. This reservation includes Sandbox Reserved 895 through Sandbox Reserved 901.

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BRPF3 PWWP binding domain 3PFS

spinqualitylabelsall models BRPF3 PWWP domain Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Overview The PWWP domain belongs to the Royal family, which consists of Tudor, chromodomain, MBT(Malignant Brain Tumor), and PWWP domains. It was first identified as a structural motif includes 100 to 130 amino acids in WHSC1 protein. The name PWWP comes after its very conservative sequence, Pro-Trp-Trp-Pro located at its β2 region. This domain is mainly related to the recognition of methylated histone tail lysine and related to the epigenetic regulation of genes. Its similar protein, BRPF1 PWWP domain presents on actively transcribing cells and we may assume that 3pfs also do similar works. Function The PWWP domain is also used for protein-protein interaction. This domain also may have nonspecific interaction with a DNA strand, using its abundant lysine and arginine residues. Nonspecific binding The PWWP domains have a significant amount of basic residues. 3pfs also has 11 lysine residues and 12 arginine residues. These residues' sidechains would be positively charged on in vivo pH. The DNA strand phosphate backbone, which is negatively charged, is attracted to PWWP domain surface due to the nature of attraction between the opposite charges. Figure 1A: Cartoon model of 3PFS motif. β-sheets(magenta) and helixes(orange) are shown. generated in PyMOL using PDB: 3PFS Figure 1B: Lysine(yellow) and Arginine(red) residues on 3PFS surface generated in PyMOL using PDB: 3PFS Methyl-lysine reader PWWP domains are one of epigenetic regulators which recognize specific lysine residues which are methylated. Even though there is no detailed research on 3pfs, it is assumed to have similar function with BRPF1 PWWP domain which is shown to have methylated histone binding activity. With a high-throughput mass spectrometry screening, this motif is suggested as an essential motif of histone 3 lysine 36 trimethylation binding. The β-strands and Pro-Trp-Trp-Pro motif form hydrophobic cavity, which is the binding site of methylated lysines. Since the aromatic cage is a common structure in the Royal family, it can be a common tool for methylated lysine binding. Structure Two disticntive The first proline affects the stability and aggregation of the protein. The proline gives more stability and oligomerization to the protein, compared to the alanine at the same position. It has two distinctive substructural motifs: β-barrel at the N-terminal region and helixes at C-terminal region. The β-barrel is a very conservative feature of PWWP domains and it is composed of 5 β-strands. 3pfs has 3 helixes which are little more than many of its relatives. The stability of domain comes from both inter-substructure and intra-substructure interactions including hydrogen bonds and polar interactions. Evolutionary conservations PWWP domain is only found in eukaryotes, from a yeast to a human. The number of PWWP containing protein is also varying on species; the human has 20. The loyal family has a common structural characteristic, three conserved β-strands. The PWWP domain is also believed to be evolved from a common ancestor which had 3 β-strands. The most conservative section is the PWWP sequence, which it is named after. Therapheutic features There is no research on the relationship between BRPF3 PWWP domain and any human disease. However, its sibling gene BRPF2 PWWP domain is associated with schizophrenia and bipolar affective disorder. This is a sample scene created with SAT to color by Group, and another to make a transparent representation of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.