The crystal structure at 4.8 angstrom resolution of the reaction center-light harvesting 1 (RC-LH1) core complex from Rhodopseudomonas palustris shows the reaction center surrounded by an oval LH1 complex that consists of 15 pairs of transmembrane helical alpha- and beta-apoproteins and their coordinated bacteriochlorophylls. Complete closure of the RC by the LH1 is prevented by a single transmembrane helix, out of register with the array of inner LH1 alpha-apoproteins. This break, located next to the binding site in the reaction center for the secondary electron acceptor ubiquinone (UQB), may provide a portal through which UQB can transfer electrons to cytochrome b/c1.

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Protein lysine methyltransferases are important regulators of epigenetic signaling. These enzymes catalyze the transfer of donor methyl groups from S-adenosylmethionine to specific acceptor lysines on histones, leading to changes in chromatin structure and transcriptional regulation. These enzymes also methylate nonhistone protein substrates, revealing an additional mechanism to regulate cellular physiology. The oncogenic protein SMYD2 represses the functional activities of the tumor suppressor proteins p53 and Rb, making it an attractive drug target. Here we report the discovery of AZ505, a potent and selective inhibitor of SMYD2 that was identified from a high throughput chemical screen. We also present the crystal structures of SMYD2 with p53 substrate and product peptides, and notably, in complex with AZ505. This substrate competitive inhibitor is bound in the peptide binding groove of SMYD2. These results have implications for the development of SMYD2 inhibitors, and indicate the potential for developing novel therapies targeting this target class.

Single assemblies of the intact light-harvesting complex LH2 from Rhodopseudomonas acidophila were bound to mica surfaces at 300 K and examined by observing their fluorescence after polarized light excitation. The complexes are generally not cylindrically symmetric. They act like elliptic absorbers, indicating that the high symmetry found in crystals of LH2 is not present when the molecules are immobilized on mica. The ellipticity and the principal axes of the ellipses fluctuate on the time scale of seconds, indicating that there is a mobile structural deformation. The B850 ring of cofactors shows significantly less asymmetry than B800. The photobleaching strongly depends on the presence of oxygen.The light-harvesting complexes are essential to photosynthesis in plants and bacteria. They absorb light from the sun and efficiently transport the photon energy to chemically reactive centers. The spectroscopic properties of the complex LH2 from photosynthetic bacteria, Rhodopseudomonas acidophila strain 10050, whose structure at atomic resolution was determined by Cogdell and coworkers (1), have been reviewed recently (2). The complex is notable for its high symmetry arrangement of the nine ␣␤-dipeptides that form the scaffold that holds the associated bacteriochlorophyll (Bchl) cofactors in place. These cofactors form into two rings that have approximate 9-fold rotation symmetry. The B800 ring consists of nine monomeric Bchls located, peripherally, between the ␤-apoproteins and closest to the N-terminal ends, whereas B850 consists of nine pairs of Bchls each associated with one ␣␤-dipeptide (1). Light absorbed in the B800 ring is transferred to B850 in less than a picosecond. In vivo the energy is transferred from B850 to the complex LH1, which also has high symmetry, and from there to a reaction center where charge separation occurs. Properties of excitations in extended systems depend on the interplay between the nuclear motions that tend to localize excitations, and the delocalizing effect of the interaction between the cofactors (3). Therefore the nature of the excitations present in the LH1 and LH2 complexes must depend not only on the static or average structures but also on the structural fluctuations that occur in solution at ambient temperature.Single molecule methods are well suited for the examination of the slow structural fluctuations (4), which are representative of the rough energy landscapes of macromolecules. Fluctuations occurring on the microsecond to minutes time scales would be manifest in conventional bulk spectroscopies as a quasistatic inhomogeneous broadening. Single macromolecules can be studied by means of fluorescent probes. Fluctuations of the macromolecular structure and orientation can result in intensity, lifetime and spectral changes of the probe fluorescence. Such methods were used to examine protein dynamics (5-7), enzyme reactions (8, 9) and nucleic acid motions (10, 11). In the case of the light-harvesting complexes a fluorescent probe is unnecessary because the intrinsic...