X-ray structure of potato epoxide hydrolase sheds light on substrate specificity in plant enzymes

Epoxide hydrolases catalyze the conversion of epoxides to diols. The known functions of such enzymes include detoxification of xenobiotics, drug metabolism, synthesis of signaling compounds, and intermediary metabolism. In plants, epoxide hydrolases are thought to participate in general defense systems. In the present study, we report the first structure of a plant epoxide hydrolase, one of the four homologous enzymes found in potato. The structure was solved by molecular replacement and refined to a resolution of 1.95 Å. Analysis of the structure allows a better understanding of the observed substrate specificities and activity. Further, comparisons with mammalian and fungal epoxide hydrolase structures reported earlier show the basis of differing substrate specificities in the various epoxide hydrolase subfamilies. Most plant enzymes, like the potato epoxide hydrolase, are expected to be monomers with a preference for substrates with long lipid-like substituents of the epoxide ring. The significance of these results in the context of biological roles and industrial applications is discussed

Crystal structures of T cell receptor β chains related to rheumatoid arthritis

The crystal structures of the Vβ17+ β chains of two human T cell receptors (TCRs), originally derived from the synovial fluid (SF4) and tissue (C5–1) of a patient with rheumatoid arthritis (RA), have been determined in native (SF4) and mutant (C5–1F104→Y/C187→S) forms, respectively. These TCR β chains form homo-dimers in solution and in crystals. Structural comparison reveals that the main-chain conformations in the CDR regions of the C5–1 and SF4 Vβ17 closely resemble those of a Vβ17 JM22 in a bound form; however, the CDR3 region shows different conformations among these three Vβ17 structures. At the side-chain level, conformational differences were observed at the CDR2 regions between our two ligand-free forms and the bound JM22 form. Other significant differences were observed at the Vβ regions 8–12, 40–44, and 82–88 between C5–1/SF4 and JM22 Vβ17, implying that there is considerable variability in the structures of very similar β chains. Structural alignments also reveal a considerable variation in the Vβ–Cβ associations, and this may affect ligand recognition. The crystal structures also provide insights into the structure basis of T cell recognition of Mycoplasma arthritidis mitogen (MAM), a superantigen that may be implicated in the development of human RA. Structural comparisons of the Vβ domains of known TCR structures indicate that there are significant similarities among Vβ regions that are MAM-reactive, whereas there appear to be significant structural differences among those Vβ regions that lack MAM-reactivity. It further reveals that CDR2 and framework region (FR) 3 are likely to account for the binding of TCR to MAM