Cyclic hexapeptide crystal

A number of substances of the ferrichrome family, containing three hydroxamic acid groups coordinated to a central ferric ion, have been isolated, mainly from microbial sources. These compounds contain a cyclic hexapeptide. Crystal structures for ferrichrome A, cyc/o[LSer-LSer-Gly-Tri ((5-N-methylglutaconyl-5-N-hydroxy-Orn)] (Figs. 11 and 12) (Zalkin et al, 1966), the isomorphous alumichrome A (van der Helm et ai, 1980), and more recently ferrichrysin [LSer-LSer-Gly-tri(5-JV-acetyl- -N-hydroxy-Orn)] (Norrestam et al, 1975) and ferrichrome (Loghry and van der Helm, 1978) have been determined and show that the molecules are essentially isostruc-tural. In these molecules, the ferric ion has approximate octahedral coordination to the six oxygen atoms of the three 5-N-acetyl-5-N-hydroxy or the... 

From a structural point of view the OPLS results for liquids have also shown to be in accord with available experimental data, including vibrational spectroscopy and diffraction data on, for Instance, formamide, dimethylformamide, methanol, ethanol, 1-propanol, 2-methyl-2-propanol, methane, ethane and neopentane. The hydrogen bonding in alcohols, thiols and amides is well represented by the OPLS potential functions. The average root-mean-square deviation from the X-ray structures of the crystals for four cyclic hexapeptides and a cyclic pentapeptide optimized with the OPLS/AMBER model, was only 0.17 A for the atomic positions and 3% for the unit cell volumes. 

We have been more concerned with the nature of the water around proteins and peptides. To this end we have investigated the structure and energetics of the solvent, both ordered and disordered around the enzyme lysozyme, in the triclinic crystal[l7d]. In addition to lysozyme, we have characterized the water structure and fluctuations in the crystal of a cyclic hexapeptide, (L-Ala-L-Pro-D-Phe)9[20]. and studied the effect of solvent on the conformation of the dipeptide of alanine[2l] and on the equilibria between extended and helical alanine polypeptides such as those discussed in the previous section[22]. The latter systems simulate aqueous solution conditions rather than crystalline environment. 

Fig. 7.2 Tlie crystal structure of mammalian Ser/Thr protein phosphatase-1, complexed with the toxin mycrocystin was determined at 2.1 A resolution. PPl has a single domain with a fold, distinct from that of the protein tyrosine phosphatases. The Ser/Thr protein phosphatase-1, is a metalloenzyme with two metal ions positioned at the active site with the help of a p-a-p-o-p scaffold. A dinuclear ion centre consisting of Mn2+ And Fe2+ g situated at the catalytic site that binds the phosphate moiety of the substrate. Ser/Thr phosphatases, PPl and PP2A, are inhibited by the membrane-permeable ocadaic acid and by cyclic hexapeptides, known as microcystins. The toxin molecule is depicted as a ball-and-stick structure. On the left and on the ri t, two different views of the same molecule are shown. Microcystin binds to three distinct regions of the phosphatase to the metaLbinding site, to a hydrophobic groove, and to the edge of a C-terminal groove in the vicinity of the active site. At the surface are binding sites for substrates and inhibitors. These ribbon models are reproduced vnth permission of the authors and Nature from ref. 9.

Crystal structures have been determined of several ferrichromes. Most of this work was performed by van der Helm and coworkers. The crystal structures of the members of this siderophore family can be superposed and a root-mean-square deviation of the 49 atoms, which are common to all members, is obtained of approximately 0.30 A. A comparison of the conformational angles around the cyclic hexapeptide ring shows differences of not more than 25°. This indicates that the structures and conformations are not the same but that they are similar with some conformational freedom. In all structures, the iron coordination site is on one side of the molecule, the coordination of the metal is K-cis, and the conformation of the amino acids is L. A (II) bend and a (I) bend of the cyclic peptide skeleton is found. In addition, extensive conformational analyses of siderophores in solution were performed by Lhnas and coworkers employing H andNMR. ... 

Kubik and co-workers have developed a series of highly effective anion receptors based upon cyclic peptides. Cyclic hexapeptide receptors such as 17 consist of alternately linked L-proline and 6-aminopicolinic acid subunits [25]. A 1 1 binding stoichiometry for 17 and the sodium salt of ben-zenesulfonate was confirmed by a Job plot but in the case of the halide and sulfate sodium salts 2 1 host/guest complexes were found. This was confirmed by electrospray mass spectrometry and in the case of iodide a crystal structure of the 2 1 complex was obtained where the iodide was sandwiched between two cyclic hexapeptide receptors. 

A new phenomenon is introduced with the cyclic hexapeptides in that the same compound can assume a number of different conformations. For example, each unit cell in the crystal of cyclic hexaglycine contains four different conformers of the molecule (Karle and Karle, 1963). Each conformer has all-trans planar peptide groups, but only one conformer contains intramolecular hydrogen bonds, a pair of parallel 4 1 bonds (Fig. 9). Two of the conformers contain a center of symmetry coincident with centers in the crystal the conformer with the transannular hydrogen bonds also contains a center, although it is not required by the symmetry elements of the crystal and the fourth conformer is asymmetric. The centers of symmetry in the cyclo Gly)e molecules are possible since glycine residues do not contain asymmetric C atoms. 

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