A combined computational and experimental investigation of the [2Fe–2S] cluster in biotin synthase

Biotin synthase was the first example of what is now regarded as a distinctive enzyme class within the radical S-adenosylmethionine superfamily, the members of which use Fe/S clusters as the sulphur source in radical sulphur insertion reactions. The crystal structure showed that this enzyme contains a [2Fe–2S] cluster with a highly unusual arginine ligand, besides three normal cysteine ligands. However, the crystal structure is at such a low resolution that neither the exact coordination mode nor the role of this exceptional ligand has been elucidated yet, although it has been shown that it is not essential for enzyme activity. We have used quantum refinement of the crystal structure and combined quantum mechanical and molecular mechanical calculations to explore possible coordination modes and their influences on cluster properties. The investigations show that the protonation state of the arginine ligand has little influence on cluster geometry, so even a positively charged guanidinium moiety would be in close proximity to the iron atom. Nevertheless, the crystallised enzyme most probably contains a deprotonated (neutral) arginine coordinating via the NH group. Furthermore, the Fe···Fe distance seems to be independent of the coordination mode and is in perfect agreement with distances in other structurally characterised [2Fe–2S] clusters. The exceptionally large Fe···Fe distance found in the crystal structure could not be reproduced

Sexual dimorphism in cancer.

The incidence of many types of cancer arising in organs with non-reproductive functions is significantly higher in male populations than in female populations, with associated differences in survival. Occupational and/or behavioural factors are well-known underlying determinants. However, cellular and molecular differences between the two sexes are also likely to be important. In this Opinion article, we focus on the complex interplay that sex hormones and sex chromosomes can have in intrinsic control of cancer-initiating cell populations, the tumour microenvironment and systemic determinants of cancer development, such as the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment

Large-scale continuous process to vitrify nuclear defense waste: operating experience with nonradioactive waste

The developmental program underway at SRL has demonstrated the vitrification process proposed for the sludge processing facility of the DWPF on a large scale. DWPF design criteria for production rate, equipment lifetime, and operability have all been met. The expected authorization and construction of the DWPF will result in the safe and permanent immobilization of a major quantity of existing high level waste. 11 figures, 4 tables

Savannah River Laboratory's operating experience with glass melters

The Department of Energy, with recommendations from the Du Pont Company, is proposing that a Defense Waste Processing Facility be constructed at the Savannah River Plant to immobilize radioactive The immobilization process is designed around the solidification of waste sludge in borosilicate glass. The Savannah River Laboratory, who is responsible for the solidification process development program, has completed an experimental program with one large-scale glass melter and just started up another melter. Experimental data indicate that process requirements can easily be met with the current design. 7 figures