With a pace of about twice the observed rate of global warming, the temperature on the Qinghai-Tibetan Plateau (Earth's 'third pole') has increased by 0.2°C per decade over the past 50 years, which results in significant permafrost thawing and glacier retreat. Our review suggested that warming enhanced net primary production and soil respiration, decreased methane (CH 4 ) emissions from wetlands and increased CH 4 consumption of meadows, but might increase CH 4 emissions from lakes. Warming-induced permafrost thawing and glaciers melting would also result in substantial emission of old carbon dioxide (CO 2 ) and CH 4 . Nitrous oxide (N 2 O) emission was not stimulated by warming itself, but might be slightly enhanced by wetting. However, there are many uncertainties in such biogeochemical cycles under climate change. Human activities (e.g. grazing, land cover changes) further modified the biogeochemical cycles and amplified such uncertainties on the plateau. If the projected warming and wetting continues, the future biogeochemical cycles will be more complicated. So facing research in this field is an ongoing challenge of integrating field observations with process-based ecosystem models to predict the impacts of future climate change and human activities at various temporal and spatial scales. To reduce the uncertainties and to improve the precision of the predictions of the impacts of climate change and human activities on biogeochemical cycles, efforts should focus on conducting more field observation studies, integrating data within improved models, and developing new knowledge about coupling among carbon, nitrogen, and phosphorus biogeochemical cycles as well as about the role of microbes in these cycles.

Orotidine 5 -monophosphate decarboxylase catalyzes the conversion of orotidine 5 -monophosphate to uridine 5 -monophosphate, the last step in biosynthesis of pyrimidine nucleotides. As part of a Structural Genomics Initiative, the crystal structures of the ligand-free and the6-azauridine 5 -monophosphate-complexed forms have been determined at 1.8 and 1.5 Å, respectively. The protein assumes a TIM-barrel fold with one side of the barrel closed off and the other side binding the inhibitor. A unique array of alternating charges (Lys-Asp-Lys-Asp) in the active site prompted us to apply quantum mechanical and molecular dynamics calculations to analyze the relative contributions of ground state destabilization and transition state stabilization to catalysis. The remarkable catalytic power of orotidine 5 -monophosphate decarboxylase is almost exclusively achieved via destabilization of the reactive part of the substrate, which is compensated for by strong binding of the phosphate and ribose groups. The computational results are consistent with a catalytic mechanism that is characterized by Jencks's Circe effect.O rotidine 5Ј-monophosphate decarboxylase (ODCase) (EC 4.1.1.23) formally catalyzes the exchange of CO 2 for a proton at the C 6 position to form uridine 5Ј-monophosphate (UMP) (1). The intermediate implied by this description consists of a C 6 -carbanion, the conjugate base of the UMP carbon acid. The ODCase reaction is unique in biological decarboxylation reactions in that the carbanion intermediate is not stabilized by conjugation interactions and, thus, the reaction rate is exceptionally slow in aqueous solution (2). The remarkable catalytic power of ODCase, which accelerates the reaction by 17 orders of magnitude over the aqueous process, has fascinated chemists and biochemists alike, leading to a number of proposals of mechanisms with novel features (3-7). However, as more results accumulated for this class of enzymes, possibilities for the mechanism became increasingly limited as cofactors and catalytic groups continued to be excluded from consideration (8-10). The high-resolution x-ray structure of ODCase from Methanobacterium thermoautotrophicum reveals that the mechanism is almost fully characterized by the formal description, along with electrostatic features of the enzyme's active site that provide selective destabilization of the orotidine group. In what follows, we report the results from a joint experimental and theoretical investigation, providing a mechanism that involves significant ground state destabilization effects in enzyme catalysis (11).The key to ODCase's catalytic power is its ability to utilize a phenomenon, which we classify as electrostatic stress [following Fersht's description of ''stress'' in catalysis (12)]. Although binding of the orotidine 5Ј-monophosphate (OMP) results in significant stabilizing interactions with the phosphate and ribose in the active site as revealed by the x-ray structural analysis, electrostatic interactions between the orotate group and ODCase is strongl...

In eukaryotic cells, the SH2 and PTB domains mediate protein-protein interactions by recognizing phosphotyrosine residues on target proteins. Here we make the unexpected finding that the C2 domain of PKCdelta directly binds to phosphotyrosine peptides in a sequence-specific manner. We provide evidence that this domain mediates PKCdelta interaction with a Src binding glycoprotein, CDCP1. The crystal structure of the PKCdelta C2 domain in complex with an optimal phosphopeptide reveals a new mode of phosphotyrosine binding in which the phosphotyrosine moiety forms a ring-stacking interaction with a histidine residue of the C2 domain. This is also the first example of a protein Ser/Thr kinase containing a domain that binds phosphotyrosine.