The CTP-binding domain is disengaged from the DNA-binding domain in a cocrystal structure of Bacillus subtilis Noc–DNA complex

In Bacillus subtilis, a ParB-like nucleoid occlusion protein (Noc) binds specifically to Noc-binding sites (NBSs) on the chromosome to help coordinate chromosome segregation and cell division. Noc does so by binding to CTP to form large membrane-associated nucleoprotein complexes to physically inhibit the assembly of the cell division machinery. The site-specific binding of Noc to NBS DNA is a prerequisite for CTP-binding and the subsequent formation of a membrane-active DNA-entrapped protein complex. Here, we solve the structure of a C-terminally truncated B. subtilis Noc bound to NBS DNA to reveal the conformation of Noc at this crucial step. Our structure reveals the disengagement between the N-terminal CTP-binding domain and the NBS-binding domain of each DNA-bound Noc subunit; this is driven, in part, by the swapping of helices 4 and 5 at the interface of the two domains. Site-specific crosslinking data suggest that this conformation of Noc-NBS exists in solution. Overall, our results lend support to the recent proposal that parS/NBS binding catalyzes CTP binding and DNA entrapment by preventing the reengagement of the CTP-binding domain and the DNA-binding domain from the same ParB/Noc subunit

CLINICAL CASE OF A MASSIVE ISOLA TED METASTATIC ADRENAL LESION IN COLORECT AL CANCER

AbstractThe liver, lungs, parietal and visceral peritoneum have traditionally been considered to be the main target organs of metastatic colorectal cancer. The isolated adrenal metastasis in colorectal cancer is rare, in the literature there are single observations of clinical cases of successful surgical treatment of such patients. This article presents the clinical observation of successful surgical treatment of patients with colorectal cancer with massive isolated adrenal metastases

PROGNOSTIC SIGNIFICANCE OF nm23 PROTEIN IN THE TUMORS OF PATIENTS WITH COLORECTAL CANCER

Purpose. Study of expression of protein nm23 inprimary and secondary foci of colorectal cancer (CRC) taking in consideration the clinical and morphological features of the disease and the possibility of predicting the risk of distant metastases. Material and methods. The study included postoperative material of 264 CRC patients with I–IV stages of cancer. Immunohistochemical staining performed by biotin-streptavidin immunoperoxidase method on the paraffin tissue sections of primary colon tumors and their metastases in lymph nodes and liver using antibodies against nm23 protein (H‑1 and H‑2) (“Dako”, Denmark). The results were evaluated by semiquantitative method based on the staining intensity and the number of antigen-positive cells and localization of immunoreactivity in cancer cells.Results. During the immunohistochemical study of primary tumors of the colon the increase of the accumulation of nm23 protein was observed in 53.4% (141/264) studied cases. In nmtastasis of CRC the main patterns of expression of a marker characteristic of the corresponding primary tumors was preserved. Survival curves, computed according to the method of Kaplan-Meyer showed that patients with nm23‑positive staining of tumors show a lower 5‑year overall survival than patients with negative immunoreactivity in the tumor. Indicators of disease-free survival in patients with CRC also deteriorated in nm23‑negative status of tumors compared to nm23‑positive status.Conclusion. The overexpression of nm 23 protein were freqently detected in metastasizing primary tumors of colon and their liver metastases and was associated with a high risk of developing distant metastases, and poor outcome of the disease and the deterioration of the postoperative overall and disease-free survival of CRC patients. A high expression level of this marker is a sign of unfavorable prognosis for CRC patients

Total synthesis of the antimalarial ascidian natural product albopunctatone

The first approaches to the 10′-anthronyl-2-anthraquinone skeleton have been devised, allowing two syntheses of the marine natural product albopunctatone. Both routes involve regioselective addition of a nucleophilic masked anthraquinone to a protected chrysazin derivative; the best affords albopunctatone in five steps and 35% overall yield. Albopunctatone exhibits potent inhibitory activity against Plasmodium falciparum and negligible toxicity to a range of other microbial pathogens and mammalian cells