X-ray studies on crystalline complexes involving amino acids and peptides. XXXIX. crystal structures of malonic acid complexes of DL- and L-histidine. preservation of aggregation pattern on reversal of chirality

The malonic acid complexes of DL- and L-histidine are made up of zwitterionic positively charged histidinium ions and semimalonate (hydrogen malonate) ions. They crystallise in space groups P2(1)/n and P2(1), respectively, with nearly the same unit-cell parameters. The molecules aggregate in the two complexes in a remarkably similar manner. The two sets of crystallographically independent molecules are related by a pseudo-glide plane. This pseudo-symmetry is almost exact except in the case of the alpha-carboxylate group and, to some extent, the alpha-C and the alpha-N atoms. Preservation of the aggregation pattern to such an extent on the reversal of chirality of half the amino-acid molecules is observed for the first time in amino-acid complexes. This is achieved at the cost of considerable conformational strain in one of the two histidinium ions in the L-histidine complex

X-ray studies on crystalline complexes involving amino acids and peptides. XL. Conformational variability, recurring and new features of aggregation, and effect of chirality in the malonic acid complexes of DL- and L-arginine

The crystal structures of the complexes of malonic acid with DL- and L-arginine, which contain positively charged argininium ions and negatively charged semimalonate ions, further demonstrate the conformational flexibility of amino acids. A larger proportion of folded conformations than would be expected on the basis of steric consideration appears to occur in arginine, presumably because of the requirements of hydrogen bonding. The aggregation pattern in the DL-arginine complex bears varying degrees of resemblance to patterns observed in other similar structures. An antiparallel hydrogenbonded dimeric arrangement of arginine, and to a lesser extent lysine, is a recurring motif. Similarities also exist among the structures in the interactions with this motif and its assembly into larger features of aggregation. However, the aggregation pattern observed in the L-arginine complex differs from any observed so far, which demonstrates that all the general patterns of amino-acid aggregation have not yet been elucidated. The two complexes represent cases where the reversal of the chirality of half the amino-acid molecules leads to a fundamentally different aggregation pattern

X-ray studies on crystalline complexes involving amino acids and peptides. XXXVIII. Crystal structures of the complexes of L-arginine and L-histidine with glutaric acid and a comparative study of amino acid-glutaric acid complexes

The complexes of glutaric acid with l-arginine and l-histidine (two crystal forms) exhibit different stoichiometries and ionization states. The aggregation patterns in two of the crystals are remarkably similar to those observed earlier in similar structures, while the pattern in the remaining one has not been seen earlier. The variability in the ionization state and stoichiometry observed in amino acid±dicarboxylic acid complexes appears to represent subtle differences in the response of a molecule to the presence in its neighbourhood of another type of molecule. The glutaric acid molecules (or glutarate or semiglutarate ions) in their complexes and in other crystals favour a fully extended conformation, albeit with frequent departures from it. The change in the chirality of the component molecules in the complex could lead to drastic changes in the aggregation pattern; alternatively, the effects of the change are accommodated through small adjustments in essentially the same pattern

Effect of stabilizing additives on the structure and hydration of proteins: a study involving monoclinic lysozyme

In pursuance of a long-range programme on the hydration, mobility and action of proteins, the structural basis of the stabilizing effect of sugars and polyols is being investigated. With two crystallographically independent molecules with slightly different packing environments in the crystal, monoclinic lysozyme constitutes an ideal system for exploring the problem. The differences in the structure and hydration of the two molecules provide a framework for examining the changes caused by stabilizing additives. Monoclinic crystals were grown under native conditions and also in the presence of 10% sucrose, 15% trehalose, 10% trehalose, 10% sorbitol and 5% glycerol. The crystal structures were reÆned at resolutions ranging from 1.8 to 2.1 A . The average B values, and hence the mobility of the structure, are lower in the presence of additives than in the native crystals. However, a comparison of the structures indicates that the effect of the additives on the structure and the hydration shell around the protein molecule is considerably less than that caused by differences in packing. It is also less than that caused by the replacement of NaNO3 by NaCl as the precipitant in the crystallization experiments. This result is not in conformity with the commonly held belief that additives exert their stabilizing effect through the reorganization of the hydration shell, at least as far as the ordered water molecules are concerned

X-ray studies on crystalline complexes involving amino acids and peptides. XLI. Commonalities in aggregation and conformation revealed by the crystal structures of the pimelic acid complexes of L-arginine and DL-lysine

The complexes of l-arginine and dl-lysine with pimelic acid are made up of singly positively charged zwitterionic amino acid cations and doubly negatively charged pimelate ions in a 2:1 ratio. In both structures, the amino acid molecules form two fold symmetric or centrosymmetric pairs that are stabilized by hydrogen bonds involving -amino and -carboxylate groups. In the l-arginine complex, these pairs form columns along the shortest cell dimension, stabilized by intermolecular hydrogen bonds involving -amino and -carboxylate groups. The columns are connected by hydrogen bonds and water bridges to give rise to an amino acid layer. Adjacent layers are then connected by pimelate ions. Unlike molecular ions aggregate into alternating distinct layers in the dl-lysine complex. In the amino acid layer, hydrogen-bonded lysinium dimers related by a glide plane are connected by hydrogen bonds involving -amino and -carboxylate groups into head to tail sequences. Interestingly, the aggregation pattern observed in l-arginine hemipimelate monohydrate is very similar to those in dl-arginine formate dihydrate, dl-arginine acetate monohydrate and l-arginine hemiglutarate monohydrate. Similarly, the aggregation of amino acid molecules is very similar in dl-lysine hemipimelate 0.53-hydrate, dl-lysine formate and dl-lysine hydrochloride. The complexes thus demonstrate how, in related structures, the effects of a change in composition, and sometimes even those of reversal in chirality, can be accommodated by minor adjustments in essentially the same aggregation pattern. It also transpires that the conformation of the argininium ion is the same in the four argininium complexes; the same is true about the conformation of the lysinium ion in the three lysinium complexes. This result indicates a relation between, and mutual dependence of, conformation and aggregation