Sequence analysis suggests that it belongs to the CRABP family in the FABP superfamily. The X-ray structure at 1.28 angstrom Enzastaurin clinical trial resolution shows the FABP beta-barrel fold, with a fatty acid inside the barrel that makes a relatively short hydrogen bond Inhibitors,Modulators,Libraries to Tyr128 and shows a double bond between C9 and C10 but that is disordered beyond C12. Mass-spectrometric studies identified this fatty acid as palmitoleic Inhibitors,Modulators,Libraries acid, confirming the double bond between C9 and C10 and establishing a length of 16 C atoms in the aliphatic chain. This acid was caught inside during the culture in Escherichia coli and therefore is not necessarily linked to the biological activity. Inhibitors,Modulators,Libraries The Tyr128Phe mutant was unable to activate the Na+/Ca2+ exchanger and the corresponding crystal structure showed that without the hydrogen bond to Tyr128 the palmitoleic acid inside the barrel becomes disordered.
Native mass-spectrometric analysis confirmed a lower occupancy of the fatty acid in the Tyr128Phe mutant. The correlation between (i) the lack of activity of the Tyr128Phe mutant, (ii) Inhibitors,Modulators,Libraries the lower occupancy/disorder of the bound palmitoleic acid and (iii) the mass-spectrometric studies of ReP1-NCXSQ suggests that the transport of a fatty acid is involved in regulation of the NCXSQ1 exchanger, providing a novel insight into the mechanism of its regulation. In order to identify the biologically active ligand, additional high-resolution mass-spectrometric studies of the ligands bound to ReP1-NCXSQ were performed after incubation with squid nerve vesicles both with and without MgATP.
These studies clearly identified AV-951 palmitic acid as the fatty acid involved in regulation of the Na+/Ca2+ exchanger from squid nerve.
The spatial distribution of radiation damage (assayed by increases in atomic B factors) to thaumatin and urease crystals at temperatures ranging from 25 to 300 K is reported. The nature of the damage changes dramatically at approximately 180 K. Above this temperature the role of solvent diffusion is apparent in thaumatin crystals, as solvent-exposed turns and loops are especially sensitive. In urease, a flap covering the active site is the most sensitive part of the molecule and nearby loops show enhanced sensitivity. Below 180 K sensitivity is correlated with poor local packing, especially in thaumatin.
At all temperatures, the component of the damage that is spatially uniform within the unit cell accounts for more than half of the total increase in the atomic B factors and correlates with changes in mosaicity. This component may arise from lattice-level, NSC 737664 rather than local, disorder. The effects of primary structure on radiation sensitivity are small compared with those of tertiary structure, local packing, solvent accessibility and crystal contacts.
Unrestrained refinement is stable for the vast majority of atoms when working at atomic resolution.