The c-jun N-terminal kinase (JNK) signaling pathway is regulated by JNK-interacting protein-1 (JIP1), which is a scaffolding protein assembling the components of the JNK cascade. Overexpression of JIP1 deactivates the JNK pathway selectively by cytoplasmic retention of JNK and thereby inhibits gene expression mediated by JNK, which occurs in the nucleus. Here, we report the crystal structure of human JNK1 complexed with pepJIP1, the peptide fragment of JIP1, revealing its selectivity for JNK1 over other MAPKs and the allosteric inhibition mechanism. The van der Waals contacts by the three residues (Pro157, Leu160, and Leu162) of pepJIP1 and the hydrogen bonding between Glu329 of JNK1 and Arg156 of pepJIP1 are critical for the selective binding. Binding of the peptide also induces a hinge motion between the Nand C-terminal domains of JNK1 and distorts the ATPbinding cleft, reducing the affinity of the kinase for ATP. In addition, we also determined the ternary complex structure of pepJIP1-bound JNK1 complexed with SP600125, an ATP-competitive inhibitor of JNK, providing the basis for the JNK specificity of the compound.

The catalyzed intramolecular hydroamination of carbon± carbon multiple bonds is one of the most important methods for the synthesis of nitrogen heterocycles. [1] Of the variety of metal-based catalysts for this transformation, complexes of the lanthanides appear uniquely well suited for effecting chemoselective alkene hydroaminations under mild reaction conditions. [2, 3] The vast majority of the complexes that have found utility for this purpose are comparatively air-and moisture-sensitive metallocene derivatives. We recently disclosed that simple amido derivatives of the Group 3 metals corresponding to the formula [Ln{N(TMS) 2 } 3 ] (1; Ln ¼ lanthanide, TMS ¼ trimethylsilyl) are competent catalysts for intramolecular alkene hydroamination. [4] Herein we show that catalytic activity can be dramatically increased and cyclization diastereoselectivity improved by coordination of the active metal center to simple chelating diamide ligands (Scheme 1).As part of our previous study, [4] we noted that the addition of representive amino alkenes to catalytic quantities COMMUNICATIONS

Bis(thiophosphinic amidate) complexes (i.e., 1) of representative group 3 and lanthanide metals have been quantiatively prepared in situ from the corresponding thiophosphinic amides and Ln[N(TMS)2]3. These unusual pentacoordinate complexes exhibit very high activity as catalysts for intramolecular alkene hydroamination.

Methionine sulphoxide reductases (Msr) catalyse the reduction of oxidized methionine to methionine. These enzymes are divided into two classes, MsrA and MsrB, according to substrate specificity. Although most MsrA and MsrB exist as separate enzymes, in some bacteria these two enzymes are fused to form a single polypeptide (MsrAB). Here, we report the first crystal structure of MsrAB from Streptococcus pneumoniae (SpMsrAB) at 2.4 Å resolution. SpMsrAB consists of an N-terminal MsrA domain, a C-terminal MsrB domain and a linker. The linker is composed of 13 residues and contains one 310-helix and several hydrogen bonds interacting with both MsrA and MsrB domains. Interestingly, our structure includes the MsrB domain complexed with an SHMAEI hexa-peptide that is the N-terminal region of neighbouring MsrA domain. A kinetic analysis showed that the apparent Km of SpMsrAB for the R-form-substrate was 20-fold lower than that for the S-form substrate, indicating that the MsrB domain had a much higher affinity for the substrate than the MsrA domain. Our study reveals the first structure of the MsrAB by providing insights into the formation of a disulphide bridge in the MsrB, the structure of the linker region, and the distinct structural nature of active site of each MsrA and MsrB domain.

The authors have demonstrated highly efficient white organic light-emitting diodes (WOLEDs) by using two emissive materials as a dopant, 1,4-bis[2-(7-N-diphenyamino-2-(9,9-diethyl-9H-fluoren-2-yl)) vinyl] benzene (DAF-ph) and iridium(III) bis(5-acetyl-2-phenylpyridinato-N,C2′) acetylacetonate ((acppy)2Ir(acac)). It was found that the OLED fabricated in this study emitted a white color consisting of three primary colors (red, green, and blue). The luminance-voltage (L-V) characteristics of the WOLEDs showed the maximum luminance of 30500cd∕m2 at 14V and the maximum luminous efficiency of 38.0cd∕A, respectively. The CIEx,y coordinates of the WOLED also showed (x=0.33, y=0.40) at 10V.