Abstract: The present invention relates to crystalline human farnesyl diphosphate synthase (FPPS), to the three-dimensional structure of free FPPS as well as the three-dimensional structures of FPPS in complex with substrates such as IPP (isopentenyl diphosphate) and/or with inhibitors such as Zometa® or Aredia®. Further, methods for preparing crystals of human FPPS are described. According to the invention the crystals can be used to determine the structures of FPPS homologs mutants, complexes with ligands, FPPS crystal forms and similar molecules of unknown structure. The invention further relates to the use of FPPS crystals to select new FPPS ligands, e.g. by X-ray screening and to design and/or identify inhibitors against FPPS. Furthermore, the invention relates to NMR methods for selecting and/or identifying new low molecular weight binders to FPPS, which represent new therapeutic agents.

Abstract: 3 ?-hydroxysteroid dehydrogenase (3a-HSD) plays a central role in the metabolism and action of steroid hormones and neurosteroids (steroids synthesized in the central nervous system). The high resolution structure of human type III 3a-HSD crystallized in complex with cofactor NADP is determined by X-ray diffraction. Furthermore the active site is determined. The structure coordinates of the enzyme may be used to design and select novel classes of modulators to human type III 3a-HSD.

Abstract: An adjustable hinge for mounting a movable door element to a frame element has a plain leaf adapted to be secured to one of the elements and having at least one knuckle, a pintle passing through the knuckle along a pintle axis, and an adjustable leaf. This adjustable leaf has a plate formed with at least one knuckle aligned with the knuckle of the plain leaf and also traversed by the pintle, and a housing adapted to be secured to the other of the elements and formed with a slot receiving the plate. The slot forms a fulcrum for pivoting of the plate relative to the housing about an adjustment axis parallel to but offset from the pintle axis through a multiplicity of angularly offset positions. An adjustable element is provided for fixing the plate in the slot in any of the angularly offset positions. In addition the plate is displaceable parallel to the axis in the housing.