Human NAD(P)H:quinone oxidoreductase 1 (NQO1) is essential for the antioxidant defense system, stabilization of tumor suppressors (e.g. p53, p33, and p73), and activation of quinone-based chemotherapeutics. Overexpression of NQO1 in many solid tumors, coupled with its ability to convert quinone-based chemotherapeutics into potent cytotoxic compounds, have made it a very attractive target for anticancer drugs. A naturally occurring single-nucleotide polymorphism (C609T) leading to an amino acid exchange (P187S) has been implicated in the development of various cancers and poor survival rates following anthracyclin-based adjuvant chemotherapy. Despite its importance for cancer prediction and therapy, the exact molecular basis for the loss of function in NQO1 P187S is currently unknown. Therefore, we solved the crystal structure of NQO1 P187S. Surprisingly, this structure is almost identical to NQO1. Employing a combination of NMR spectroscopy and limited proteolysis experiments, we demonstrated that the single amino acid exchange destabilized interactions between the core and C-terminus, leading to depopulation of the native structure in solution. This collapse of the native structure diminished cofactor affinity and led to a less competent FAD-binding pocket, thus severely compromising the catalytic capacity of the variant protein. Hence, our findings provide a rationale for the loss of function in NQO1 P187S with a frequently occurring single-nucleotide polymorphism.

Finite-temperature properties are modeled for the itinerant-electron ferromagnets Fe, Co, and Ni by employing a spin-fluctuation theory where the modes are coupled by interatomic exchange interactions. Our method is based on the density functional theory using the local density approximation. The latter yields all parameters derived from constrained ground-state properties of noncollinear spin configurations to calculate ab initio the Curie temperatures, the magnetic susceptibilities, and, furthermore, the hcp-fcc phase transition of Co. Our results are in fair agreement with experimental data. [S0031-9007(96)00537-6] PACS numbers: 71.15.Mb, 75.10.Lp, 75.30.Cr, The magnetic properties of transition metals at very low temperatures are well described by spin-polarized band theory provided this is based on the density functional formalism, a rather well-tested computational method being the local density approximation [1,2]. In fact, spin-polarized band theory can be seen as the ab initio version of Stoner-Wohlfarth theory [3,4] in which the magnetic moments are brought about by the itinerant d electrons whose spins align because of intra-atomic exchange interactions. Recent reviews can be found, e.g., in [5,6].At finite temperatures, however, Stoner-Wohlfarth theory fails to account for the magnetic properties in most cases, particularly so for Fe, Co, and Ni. The reason for this is that the magnetic moments are supposed to disappear through spin-flip excitations to the Stoner continuum, a process that costs too much energy leading to unphysically high Curie temperatures and a paramagnetic susceptibility that does not describe the experimentally observed Curie-Weiss law.Awareness of low-energy excitations for explaining the magnetic phase transition arose in the seventies predominantly through the pioneering work of Moriya, Hubbard, Hasegawa, Korenman et al., Gyorffy et al.,, and others; see, for example, [13,14]. The broad consensus reached [13] was that orientational fluctuations of the local magnetization represent the essential ingredients to a thermodynamic theory. Still, the detailed approaches seemingly differed considerably; thus, for instance, Gyorffy et al.[11] emphasized a picture of disordered local moments, whereas Korenman, Murray, and Prange used a fluctuating-local-band picture [10]. In spite of the considerable progress in the formulation of the problem, actual first-principles treatments of spin fluctuations that result in hard numbers for itinerant-electron systems are still rare, a notable exception is given by the work of Staunton and Gyorffy [15].In this Letter, using an approach different from that of Staunton and Gyorffy, in particular, not making any explicit assumptions about the local degree of order, we obtain first-principles estimates for magnetic properties of 3d metals on the basis of ground-state properties using the density functional theory. Assuming the adiabatic approximation for magnetic moments, we separate slow and fast motion, the time scale for spin fluctuations being much ...

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We report results of calculations that explain in the itinerant-electron picture magnetic and electronic properties of haematite, . For this we use the local approximation to spin-density functional theory and the ASW method incorporating spin - orbit coupling and noncollinear moment arrangements. The insulating character of the compound is obtained correctly and features in the density of states connected with Fe - O hybridization correlate well with experimental features seen in direct and inverse photoemission intensities. The total energy correctly predicts the experimentally observed magnetic order of the ground state, and, using total energies of different magnetic configurations, we can give a rough estimate of the Néel temperature. We also obtain a state showing weak ferromagnetism. The rate of change is calculated for the decrease of the insulating gap when an external magnetic field is applied.