The first crystal structure of a gramicidin complex with sodium: high-resolution study of a nonstoichiometric gramicidin D-NaI complex.

The crystal structure of the nonstoichiometric complex of gramicidin D with NaI has been studied using synchrotron radiation at 100 K. The limiting resolution was 1.25 A and the R factor was 16% for 19 883 observed reflections. The general architecture of the antiparallel two-stranded gramicidin dimers in the studied crystal was a right-handed antiparallel double-stranded form that closely resembles the structures of other right-handed species published to date. However, there were several surprising observations. In addition to the significantly different composition of linear gramicidins identified in the crystal structure, including the absence of the gramicidin C form, only two cationic sites were found in each of the two independent dimers (channels), which were partially occupied by sodium, compared with the seven sites found in the RbCl complex of gramicidin. The sum of the partial occupancies of Na(+) was only 1.26 per two dimers and was confirmed by the similar content of iodine ions (1.21 ions distributed over seven sites), which was easily visible from their anomalous signal. Another surprising observation was the significant asymmetry of the distributions and occupancies of cations in the gramicidin dimers, which was in contrast to those observed in the high-resolution structures of the complexes of heavier alkali metals with gramicidin D, especially that of rubidium.

Nonstoichiometric complex of gramicidin D with KI at 0.80 A resolution.

The crystal structure of a nonstoichiometric complex of gramicidin D (gD) with KI has been determined at 100 K using synchrotron radiation. The final R factor was 0.106 for 83 988 observed reflections (Friedel pairs were not merged) collected to 0.80 A. The structure consists of four independent pentadecapeptides and numerous solvent molecules and salt ions. The general architecture of the antiparallel double-stranded gramicidin dimers in the crystal (a right-handed antiparallel DSbetaH(R) form) closely resembles that of previously published cation complexes of gD. However, a significantly different mixture of gramicidin isomers is found in the crystal of the KI complex, including partial occupancy of phenylalanine at position 11. Only three sites in each of the two crystallographically independent channels are partially occupied by potassium cations instead of the commonly observed seven sites. The sum of the partial occupancies of K(+) (1.10 per two dimers) is consistent with the sum of the iodide occupancies (1.095 over eight sites), which is also confirmed by the anomalous signal of the iodide. There was a significant asymmetry of the distribution and occupancies of cations in the crystallographically independent gramicidin channels, in contrast to the distribution found in the rubidium chloride complex with gD.

Structure of gramicidin D-RbCl complex at atomic resolution from low-temperature synchrotron data: interactions of double-stranded gramicidin channel contents and cations with channel wall.

Gramicidin D (gD) is a naturally occurring ionophoric antibiotic that forms membrane channels specific for monovalent cations. The crystal structure of the RbCl complex of gD has been determined at 1.14 A resolution from low-temperature (100 K) synchrotron-radiation data with a final R of 16%. The structure was refined with anisotropic temperature factors for all non-H atoms and with partial occupancies for many of them. The asymmetric unit in the crystal contains four crystallographically independent molecules that form two right-handed antiparallel double-stranded dimers. There are seven distinct rubidium-binding sites in each dimeric channel. The occupancy factors of Rb cations are between 0.11 and 0.35 and the total ion contents of the two crystallographically independent channels are 1.59 and 1.22 ions, respectively. Although each channel is 'chemically symmetrical', the side-chain conformations, the distributions of rubidium cations and their binding sites in the two independent channels are not. Cations are 'coordinated' by delocalized pi-electrons of three to five carbonyl groups that together with peptide backbone chains form the gramicidin channel walls. The water:cation ratio in the channel interior is four or five:one, and five or six waters separate Rb cations during their passage through the channel.

[The influence of twenty years of Rh (D) factor incompatibility immunoprophylaxis on reducing the occurrence of hemolytic disease in newborns]. / Wplyw dwudziestoletniego okresu stosowania immunoprofilaktyki w zakresie czynnika Rh (D) na zmniejszenie wystepowania choroby hemolitycznej u noworodków w aglomeracji walbrzyskiej.

The study presents the frequency of occurrence of newborn haemolitic disease caused by Rh (D) system incompatibility in the years 1980-1999. Serological incompatibility prophylaxis was introduced in 1980. Routine use of anti-D immunoglobulin has led to a significant reduction in the number of newborns with haemalitic disease caused by Rh (D) system incompatibility. In the years 1990-1999 no newborn deaths attributable to this immunization were recorded. Long-term prophylaxis has greatly reduced the occurrence of this pathology in newborns. Nonetheless, in contemporary perinatology we continue to record occasional cases of haemolitic disease in newborns caused by blood group incompatibility between mother and foetus.