Indoleamine 2,3-dioxygenase 1 (IDO1), promoting immune escape of tumors, is a therapeutic target for the cancer immunotherapy. A number of IDO1 inhibitors have been identified, but only limited structural biology studies of IDO1 inhibitors are available to provide insights on the binding mechanism of IDO1. In this study, we present the structure of IDO1 in complex with 24, a NLG919 analogue with potent activity. The complex structure revealed the imidazole nitrogen atom of 24 to coordinate with the heme iron, and the imidazoleisoindole core situated in pocket A with the 1-cyclohexylethanol moiety extended to pocket B to interact with the surrounding residues. Most interestingly, 24 formed an extensive hydrogen bond network with IDO1, which is a distinct feature of IDO1/24 complex structure and is not observed in the other IDO1 complex structures. Further structure-activity relationship, UV spectra, and structural biology studies of several analogues of 24 demonstrated that extensive hydrophobic interactions and the unique hydrogen bonding network contribute to the great potency of imidazoleisoindole derivatives. These results are expected to facilitate the structure-based drug design of new IDO inhibitors.

Keywords:Heterometallic complexes / Metal-metal interactions / Mixed-valent compounds / Electronic structure / Singlemolecule conductanceThe study of metal string complexes with 1D transition-metal frameworks began in the early 1990s. As these complexes provide great insights into metal-metal multiple bonds and may have potential applications as molecular wires, this field of research has grown in the past 20 years. As such, the electronic structures of the simplest trinuclear complexes, the supporting ligand systems, and the single-molecular conduc-

The variation of the instantaneous frequencies of bridges under moving vehicles is a problem not well studied in the literature. A theoretical framework is presented for the problem, considering the variation in frequencies for both the bridge and moving vehicle. First, the equations of motion are written for the two sub-systems. By solving the eigenvalue problem, analytical solutions in closed-form are derived from the frequencies of the vehicle and bridge that are coupled with each other. Based on this, the variation pattern, range, and dominating factors involved are studied, along with the special cases of moving mass and moving load. The results reveal that, if a moving vehicle is to be used as a tool for measuring the bridge frequencies or for detecting the bridge damages, the frequency variation caused by moving vehicles should be taken into account. Such an effect will be crucial when the vehicle mass is not negligible compared with the bridge mass or when the resonance condition is approached.

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The transcription of rice plastid psbD-psbC genes encoding photosystem II reaction center protein D2 and chlorophyll alpha-binding protein CP43 is closely regulated by light. To elucidate the sequence requirement for the light-responsive promoter of psbD-psbC operon, transcriptional analysis of the rice promoter was performed with deleted mutants and site-directed mutants in vitro. Deletion of -546 approximately -100 upstream sequences resulted in 4- to 5-fold decrease in the transcription rate. Further deletion of -99 approximately -40 conserved region of repeated sequences resulted in 2-fold decrease in the transcription rate. The core light-responsive promoter requires "-10" element but not "-35" element for accurate initiation of basal transcription. No downstream promoter element was found in the +4 approximately +111 region. The competitive gel-retardation experiments revealed the presence of DNA-binding protein in the rice chloroplasts, which interacts specifically with the -60 approximately -37 repeated sequences. Southwestern blot analysis further demonstrated that the binding factor is composed of 36-kDa polypeptide(s).