Evolution of (p)ppGpp-HPRT regulation through diversification of an allosteric oligomeric interaction

The alarmone (p)ppGpp regulates diverse targets, yet its target specificity and evolution remain poorly understood. Here, we elucidate the mechanism by which basal (p)ppGpp inhibits the purine salvage enzyme HPRT by sharing a conserved motif with its substrate PRPP. Intriguingly, HPRT regulation by (p)ppGpp varies across organisms and correlates with HPRT oligomeric forms. (p)ppGpp-sensitive HPRT exists as a PRPP-bound dimer or an apo- and (p)ppGpp-bound tetramer, where a dimer-dimer interface triggers allosteric structural rearrangements to enhance (p)ppGpp inhibition. Loss of this oligomeric interface results in weakened (p)ppGpp regulation. Our results reveal an evolutionary principle whereby protein oligomerization allows evolutionary change to accumulate away from a conserved binding pocket to allosterically alter specificity of ligand interaction. This principle also explains how another (p)ppGpp target GMK is variably regulated across species. Since most ligands bind near protein interfaces, we propose that this principle extends to many other protein–ligand interactions.</jats:p

A technological examination of ninth-tenth century AD Abbasid blue-and-white ware from Iraq, and its comparison with eighth century AD Chinese blue-and-white Sancai ware

Eight sherds of 9th -10th century AD Abbasid blue-and-white glazed earthenware, excavated in 1931 at Hira in western Iraq, were analysed using, variously, quantitative wavelength dispersive spectrometry (WDS) and energy dispersive spectrometry (EDS) in association with scanning electron microscopes (SEM), and semi-quantitative x-ray fluorescence spectrometry (XRF). In order to compare the compositions of the cobalt pigments used, the glazes of seven complete vessels of 8th century AD Chinese Tang blue-and-white sancai were also analysed semi-quantitatively using XRF. The Abbasid wares were shown to have used traditional Mesopotamian alkali-lime glazes applied to calcareous clay bodies. However, about half the glazes examined were opacified with tin oxide. The three types of blue decoration (ie raised; spreading; and flat, non-spreading) were produced using a variety of glaze formulations including a mixture of cobalt pigment with lead oxide. The sources of the ores used for the cobalt pigments have not been identified. However, the analytical data showed that the cobalt ore used for the Abbasid blue-and-white ware could be distinguished from that used for the Tang blue-and-white sancai by its higher iron content and by the presence of a significant amount of zinc. The use of cobalt blue decoration on the 9th – 10th century AD Abbasid ware was anticipated in China by 8th century AD Tang blue-and-white sancai wares. However, whether its introduction by the Abbasid potters should be seen as an independent invention that followed the introduction of tin-opacified glazes in Iraq, or whether it was influenced in some way by Chinese originals is still a problem