Crystal Structure and Substrate Specificity of PTPN12

PTPN12 is an important tumor suppressor that plays critical roles in various physiological processes. However, the molecular basis underlying the substrate specificity of PTPN12 remains uncertain. Here, enzymological and crystallographic studies have enabled us to identify two distinct structural features that are crucial determinants of PTPN12 substrate specificity: the pY+1 site binding pocket and specific basic charged residues along its surface loops. Key structurally plastic regions and specific residues in PTPN12 enabled recognition of different HER2 phosphorylation sites and regulated specific PTPN12 functions. In addition, the structure of PTPN12 revealed a CDK2 phosphorylation site in a specific PTPN12 loop. Taken together, our results not only provide the working mechanisms of PTPN12 for desphosphorylation of its substrates but will also help in designing specific inhibitors of PTPN12

Cyanobacterial population and harmful metabolites dynamics during a bloom in Yanghe Reservoir, North China

A significant outbreak of odorous and toxic cyanobacteria occurred in Yanghe Reservoir, North China, in the summer of 2007. The dominant species was Anabaena spiroides and it was accompanied with the occurrence of very high concentrations of the odor metabolite geosmin. The event included two cycles of growth of A. spiroides: the first one of approximately 16 days between 21 June and 8 July, with the peak density 70,000 cells mL−1 on 2 July, and the second smaller bloom of over 50 days between 9 July and the end of August. The bloom also included a range of species of Microcystis, predominantly M. aeruginosa, as the second largest population, which varied from 5800 cells mL−1 to 28,000 cells mL−1 in the first cycle and from 2000 cells mL−1 to 11,000 cells mL−1 in the second. Geosmin reached the peak value of 7100 ng L−1 on 3 July, which was the highest value ever reported. The average geosmin production potential for A. spiroides cells was approximately 0.1 pg cell−1, which was also very high and 85–97% of geosmin was found within the cells and in addition the dissolved geosmin did not increase even during the cyanobacterial decay period. In addition to odor metabolites, three microcystin variants MC-LR, MC-RR, MC-YR and anatoxin-a, most of which were intracellular, were detected, with MC-RR being the dominant cyanotoxin. The highest cyanotoxin concentrations were: dissolved: MC-RR 1.56 μg L−1, MC-YR 0.066 μg L−1, MC-LR 0.544 μg L−1, anatoxin-a 0.106 μg L−1; intracellular: MC-RR 70.1 μg L−1, MC-YR 3.76 μg L−1, MC-LR 24.6 μg L−1, anatoxin-a 0.184 μg L−1, and these occurred on 2 July. The correlation between geosmin and A. spiroides was excellent (R2 = 0.912), however the correlation between anatoxin-a concentrations and Anabaena densities and between MCs concentrations and Microcystis densities was not as strong. This study demonstrated the relatively complex requirement for monitoring cyanobacterial blooms in this lake in China, where both the range of odors and cyanotoxins can be produced in concentrations which can change rapidly over a short time along with the bloom composition. It also demonstrated that both odor compounds and cyanotoxins should be considered in terms of the potential hazard to public water supply when a bloom was dominated by Anabaena and Microcystis occurs.Zonglai Li, Jianwei Yu, Min Yang, Jing Zhang, Michael D. Burch and Wei Ha