Structure determination by X-ray

The situation is different for other examples—for example, the peptide hormone glucagon and a small peptide, metallothionein, which binds seven cadmium or zinc atoms. Here large discrepancies were found between the structures determined by x-ray diffraction and NMR methods. The differences in the case of glucagon can be attributed to genuine conformational variability under different experimental conditions, whereas the disagreement in the metallothionein case was later shown to be due to an incorrectly determined x-ray structure. A re-examination of the x-ray data of metallothionein gave a structure very similar to that determined by NMR. 

The HIV-l protease is a remarkable viral imitation of mammalian aspartic proteases It is a dimer of identical subunits that mimics the two-lobed monomeric structure of pepsin and other aspartic proteases. The HIV-l protease subunits are 99-residue polypeptides that are homologous with the individual domains of the monomeric proteases. Structures determined by X-ray diffraction studies reveal that the active site of HIV-l protease is formed at the interface of the homodimer and consists of two aspartate residues, designated Asp and Asp one contributed by each subunit (Figure 16.29). In the homodimer, the active site is covered by two identical flaps, one from each subunit, in contrast to the monomeric aspartic proteases, which possess only a single active-site flap. 

As was suggested in the preceding discussion, most of the arene complexes isolated by metal-atom techniques are benzene derivatives. However, heterocyclic ligands are also known to act as 5- or 6-electron donors in transition-metal 7r-complexes (79), and it has proved possible to isolate heterocyclic complexes via the metal-atom route. Bis(2,6-di-methylpyridine)Cr(O) was prepared by cocondensation of Cr atoms with the ligand at 77 K (79). The red-brown product was isolated in only 2% yield the stoichiometry was confirmed by mass spectrometry, and the structure determined by X-ray crystal-structure analysis, which supported a sandwich formulation. 

Peptoids based on a-chiral aliphatic side chains can form stable helices as well [43]. A crystal of a pentameric peptoid homooligomer composed of homochiral N-(1-cyclohexylethyl)glycine residues was grown by slow evaporation from methanol solution, and its structure determined by X-ray crystallographic methods. In the crystalline state, this pentamer adopts a helical conformation with repeating cis-... 

This chapter consists of four main sections. The first provides an overall description of the process of contemporary protein structure determination by X-ray crystallography and summarizes the current computational requirements. This is followed by a summary and examples of the use of structure-based methods in drug discovery. The third section reviews the key developments in computer hardware and computational methods that have supported the development and application of X-ray crystallography over the past forty or so years. The final section outlines the areas in which improved... 

It was not until 1981 that the first brevetoxin structure was determined (13), PbTX-2, the most plentiful of the brevetoxins, was purified to crystallinity and the structure determined by x-ray crystallography. This important first step was the result of a three-group collatoration among Clardy, Lin, and Nakanishi. The yields of the major components from 50 L of culture (ca. 5 x 10 cells) were 0.8 mg of PbTX-1, 5.0 mg of PbTX-2, and 0.4 mg of PbTX-8. The structure of PbTX-2,... 

The limited number of characterized complexes of arsine and arsenide ligands contain some similar structural motifs to those exhibited for equivalent phosphorus ligands. Coordination numbers of two, three, or four are observed with monomeric up to decameric zinc complexes structurally determined by X-ray crystallography. 

Fig. 21.1 The interactions between the bound coenzyme molecule and the amino acids at positions 47 and 369 in the / , / 2, and / 3 polymorphic variants as observed in their respective structures determined by X-ray crystallography. The dashed lines indicate possible hydrogen-bonds between the amino acids and the phosphate oxygens of the bound coenzyme molecule, NAD(H). Arg47 is substituted by a His residue in the f 2 isozyme and Arg369 is substituted by a Cys residue in the / 3 isozyme. In each case, the substitution results in a net loss of hydrogen-bonding interactions and weaker affinity for the coenzyme.

Our understanding of the importance of steric factors was initiated by structure determinations by X-ray diffraction techniques of two trans-diols of benz[a]anthracene (89), XVI and XVII, shown in Figure 12. The crystal structures showed diequatorial... 

Dicyanofuroxan (3,4-dicyano-l,2,5-oxadiazole 2-oxide), the precursor to the NCCNO (see structure 11) species, has been studied in the solid and gas phases to obtain both structural and electronic information. The solid-state structure determined by X-ray diffraction gives an orthorhombic space group PnaZ, with a= 10.2578(14), b = 10.8818(12), and c= 10.2259(15) A. There are two independent molecules with similar geometries in the asymmetric unit. The gas-phase molecule was characterized by Hel photoelectron, Hel and HLtti(3i7 photoionization, and IR spectroscopy. The... 

The selenium analogues of these 1,3,2-dithiazolyl radicals have not been extensively studied. Benzo-l,3,2-diselenazolium perchlorate 28 can be prepared from 27 in an analogous fashion to the corresponding sulfur compound55 and its structure determined by X-ray structure analysis. Unlike BDTA (1,3,2-dithiazolyl radical), reduction of 28 afforded an unstable neutral radical. No stable selenium analogues have yet been isolated (Scheme 8). 

A large variety of organotin carboxylates have been prepared, and their structures determined by X-ray diffraction. Part of the impetus for this work has been the search for anticancer drugs, and the aim of relating activity to structure. The early work on structure has been thoroughly reviewed,346 as well as recent developments,347 including the structural work on the organotin derivatives of amino acids and peptides.348... 

Figure 16. The molecular structure of the radical cation 22 +SbCl6 having a 2,3,5,6-tetrathiabicyclo[2.2.2]oct-7-ene structure, determined by X-ray... 

Metallabenzenes (M = Os, Ir) (Scheme 76) have been synthesized and their structures determined by X-ray. The compounds are planar and have NMR spectra and geometries indicative of aromatic character.240-242 Recently, osmabenzene derivatives 199 were shown to undergo electrophilic substitutions, affording nitro (200) and bromo (201) derivatives (Scheme 76).243 However, some reactions are at... 

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