Mevinolin, a fungal metabolite, was isolated from cultures of Aspergillus terreus. The structure and absolute configuration of mevinolm and its open acid form, mevinolinic acid, were determined by a combination of physical techniques.

Crystals of a 1:1 hydrogen-bonded complex between 1-methylthymine and 9-methyladenine can be grown from an aqueous solution containing equimolecular quantities of the two compounds. The crystals are monoclinic, with a--8-304, b = 6.552, c = 12.837 A, and fl--106 ° 50'. The space group is P21/m, with two base-pair complexes in the unit cell. The structure was refined with three-dimensional data taken with copper radiation. The positional coordinates and anisotropic temperature factors of the heavy atoms were obtained by least-squares analyses. The hydrogen atoms, except those of two methyl groups, were located from a three-dimensional difference Fourier synthesis. The 1-methylthymine and 9-methyladenine molecules form a planar base pair lying in a mirror plane and are connected to each other by two nearly linear hydrogen bonds, from the NH 2 group of 9-methyladenine to 0(9) of 1-methylthymine (2.846 A) and from N(3) of 1-methylthymine to N(7) of 9-methyladenine (2.924 A).This structure differs from the adenine-thymine pairing proposed by Watson & Crick, where N(3) of thymine is hydrogen bonded to N(i) of adenine. The distance between the methyl group at N(1) of 1-methylthymine and the one at N(9) of 9-methyladenine is 8-645 A, whereas this distance is 11.

A central eight-stranded beta-pleated sheet is the main feature of the polypeptide backbone folding in dihydrofolate reductase. The innermost four strands and two bridging helices are geometrically similar to but are connected in a different way from those in the dinucleotide binding domains found in nicotinamide-adenine dinucleotide-linked dehydrogenases. Methotrexate is bound in a 15-angstrom-deep cavity with the pteridine ring buried in a primarily hydrophobic pocket, although a strong interaction occurs between the side chain of aspartic acid 27 and N(1), N(8), and the 2-amino group of methotrexate.

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Human neutrophil elastase (HNE) has been implicated as a major contributor to tissue destruction in various disease states, including emphysema. The structure of HNE, at neutral pH, in complex with methoxysuccinylAla-Ala-Pro-Ala chloromethyl ketone (MSACK), has been solved and refmed to an R factor of 16.4% at 1.84-A resolution.Results are consistent with the currently accepted mechanism of peptide chloromethyl ketone inhibition of serine proteases, in that MSACK cross-links the catalytic residues His-57 and Ser-195. The structure of the HNE-MSACK complex is compared with that of porcine pancreatic elastase in complex with L-647,957, a fi-lactam inhibitor of both elastases. The distribution of positively charged residues on HNE is highiy asymmetric and may play a role in its specific association with the underlying negatively charged proteoglycan matrix of the neutrophil granules in which the enzyme is stored.