Structural insights into the C-terminus of the histone-lysine N-methyltransferase NSD3 by small-angle X-ray scattering.

NSD3 is a member of six H3K36-specific histone lysine methyltransferases in metazoans. Its overexpression or mutation is implicated in developmental defects and oncogenesis. Aside from the well-characterized catalytic SET domain, NSD3 has multiple clinically relevant potential chromatin-binding motifs, such as the proline-tryptophan-tryptophan-proline (PWWP), the plant homeodomain (PHD), and the adjacent Cys-His-rich domain located at the C-terminus.

The Automatic Solution of Macromolecular Crystal Structures via Molecular Replacement Techniques: REMO22 and Its Pipeline.

A description of REMO22, a new molecular replacement program for proteins and nucleic acids, is provided. This program, as with REMO09, can use various types of prior information through appropriate conditional distribution functions. Its efficacy in model searching has been validated through several test cases involving proteins and nucleic acids.

Structural Characterization of the Full-Length Anti-CD20 Antibody Rituximab.

Rituximab, a murine-human chimera, is the first monoclonal antibody (mAb) developed as a therapeutic agent to target CD20 protein. Its Fab domain and its interaction with CD20 have been extensively studied and high-resolution atomic models obtained by X-ray diffraction or cryo-electron microscopy are available. However, the structure of the full-length antibody is still missing as the inherent protein flexibility hampers the formation of well-diffracting crystals and the reconstruction of 3D microscope images.

How far are we from automatic crystal structure solution via molecular-replacement techniques?

Although the success of molecular-replacement techniques requires the solution of a six-dimensional problem, this is often subdivided into two three-dimensional problems. REMO09 is one of the programs which have adopted this approach. It has been revisited in the light of a new probabilistic approach which is able to directly derive conditional distribution functions without passing through a previous calculation of the joint probability distributions.

Set7 Is a H3K37 Methyltransferase in Schizosaccharomyces pombe and Is Required for Proper Gametogenesis.

Histone methylation by histone methyltransferases (HMTases) has a key role in transcriptional regulation. Discrepancies between the known HMTases and the histone lysine methylome suggest that HMTases remain to be identified. Here we report the discovery, characterization, and crystal structure of Schizosaccharomyces pombe Set7, an HMTase methylating the uncharted histone H3 lysine 37 (H3K37) mark.