The structures of the ligand-binding domains (LBD) of the wildtype androgen receptor (AR) and the T877A mutant corresponding to that in LNCaP cells, both bound to dihydrotestosterone, have been refined at 2.0 Å resolution. In contrast to the homodimer seen in the retinoid-X receptor and estrogen receptor LBD structures, the AR LBD is monomeric, possibly because of the extended C terminus of AR, which lies in a groove at the dimerization interface. Binding of the natural ligand dihydrotestosterone by the mutant LBD involves interactions with the same residues as in the wildtype receptor, with the exception of the side chain of threonine 877, which is an alanine residue in the mutant. This structural difference in the binding pocket can explain the ability of the mutant AR found in LNCaP cells (T877A) to accommodate progesterone and other ligands that the wild-type receptor cannot.

No abstract

The geometries of some 170 examples of calciumcarboxylate interactions from crystal structures of calcium complexes are reviewed. Calcium-carboxylate interactions fall into three main categories: a unidentate mode in which the Ca ion binds to only one of the carboxylate O atoms; a bidentate mode in which the carboxylate ion uses both O atoms to chelate the Ca ion; and an additional chelation mode, the a mode, that is observed when a suitable ligand for the Ca ion is attached at the a position and in which chelation of the Ca ion is achieved by use of the ct substituent together with one of the carboxylate O atoms. The three modes show distinct geometrical preferences, but in each there is a strong tendency for the Ca ion to lie near the plane of the carboxylate group. In general, there is little tendency for a Ca ion to be collinear with the C-O bond. The unidentate examples cluster on both sides of the C-O bond, with most Ca ions lying at Ca--O-C angles of about 150-170 ° on the side away from the second O atom of the carboxylate group, or 110-140 ° on the side toward the second O atom.

The crystals of most proteins or other biological macromolecules are poorly ordered and diffract to lower resolutions than those observed for most crystals of simple organic and inorganic compounds. Crystallization in the microgravity environment of space may improve crystal quality by eliminating convection effects near growing crystal surfaces. A series of 11 different protein crystal growth experiments was performed on U.S. space shuttle flight STS-26 in September 1988. The microgravity-grown crystals of γ-interferon D 1 , porcine elastase, and isocitrate lyase are larger, display more uniform morphologies, and yield diffraction data to significantly higher resolutions than the best crystals of these proteins grown on Earth.

The native anomalous phasing method will have greatest application to cases where poor occupancy or multiple substitution occurs, making direct interpretation of isomorphous difference Pattersons difficult. Alternatively, this method may be useful for locating relative origins for the binding sites from several derivatives in unfavorable space groups, such as P1. The major reasons for the success of the method are that full occupancy of the native anomalous scatterer always occurs, the number and types of binding sites are chemically defined, and the X-ray data are inherently more accurate, since no scaling is needed for anomalous pairs and lack of isomorphism never occurs.The authors wish to thank Drs B. Matthews and G. Kartha for helpful discussions. This work has been supported by NSF Grant No. GB27683 and Life Insurance Medical Research Fund No. G-70-28 Crystals of 1,8-bis(dimethylamino)naphthalene, C14HIsN2, are orthorhombic, space group P212~21, with a= 12.855 (1), b= 10.110 (1), c=9"664 (1)~ and Z=4. A complete structure determination, including refinement of the positions of the hydrogen atoms, led to an R index of 0-053 and a goodness-offit of 2.02 for 1477 reflections. The molecule adopts a conformation in which one carbon atom of each of the dimethylamino groups is eclipsed with respect to the naphthalene ring. Hindrance between the dimethylamino groups and/or resonance interactions between the dimethylamino groups and the aromatic ring are sufficiently great to distort the ring in several ways, the most conspicuous being a sizable increase in the non-bonded C(1)-.. C(8) distance (2.56 ~) compared to the C(4)-.-C(5) distance (2"44 A) and a twisting of the naphthalene ring into a considerably nonplanar conformation. IntroductionThe title compound, N,N,N',N'-tetramethyl-l,8-di- usual basic properties ('the proton sponge'; Alder, Bowman, Steele & Winterman, 1968) and for the steric effects which are expected to be encountered and their influence on the conformation that the molecule will find most favorable. Normally, there is strong resonance interaction between a dimethylamino group and an aromatic ring, so that one might expect a planar conformation to be favored (cf., e.g. Wheland, 1955). However, because of the steric difficulties for compounds such as (I), there is no reasonable possibility of bringing even one of the dimethylamino groups into the plane of the ring. Alternative possibilities include (II), where 1612 PERI INTERACTIONS the methyl groups are out of one another's way but the nitrogen lone pairs are brought face to face; (III), where the lone pairs are favorably situated relative to one another but one pair of methyl groups interferes strongly with a nitrogen atom ; and (IV), a compromise achieved at the expense of some interference between one methyl group on each nitrogen atom and the hydrogens at positions 2 and 7. A further question concerns the amount of ~z character in the C(ring)-N bonds, and whether it might be sufficient to force the nitrogen atoms into planar configurations....