The activity of proteins delivered into host cells by the Dot/Icm injection apparatus allows Legionella pneumophila to establish a niche called the Legionella-containing vacuole (LCV), which is permissive for intracellular bacterial propagation. Among these proteins, substrate of Icm/Dot transporter (SidC) anchors to the cytoplasmic surface of the LCV and is important for the recruitment of host endoplasmic reticulum (ER) proteins to this organelle. However, the biochemical function underlying this activity is unknown. Here, we determined the structure of the N-terminal domain of SidC, which has no structural homology to any protein.Sequence homology analysis revealed a potential canonical catalytic triad formed by Cys46, His444, and Asp446 on the surface of SidC. Unexpectedly, we found that SidC is an E3 ubiquitin ligase that uses the C-H-D triad to catalyze the formation of highmolecular-weight polyubiquitin chains through multiple ubiquitin lysine residues. A C46A mutation completely abolished the E3 ligase activity and the ability of the protein to recruit host ER proteins as well as polyubiquitin conjugates to the LCV. Thus, SidC represents a unique E3 ubiquitin ligase family important for phagosomal membrane remodeling by L. pneumophila.
The relief degree of land surface (RDLS) is an important factor for describing the landform at macro-scales. This study defines a concept for RDLS and applies the concept for population distribution study of the entire country. Based on the concept and macro-scale digital elevation model datum and ARC/INFO software, the RDLS at a 10 km×10 km grid size of China is extracted. This paper depicts systemically the spatial distributions of RDLS through analyzing the ratio structure and altitudinal characters of RDLS in China. The conclusions are drawn as follows: the RDLS in more than 63% of the area is less than one (1) (relative altitude is less than 500 m), reflecting the fact that most of RDLS in China is low. In general, the RDLS in the west is larger than that in the east and so is the south than that of the north in China. The RDLS decreases with the increase of longitude and latitude and the change of RDLS at the latitudes of 28°N, 35°N, 42°N, as well as at the longitudes of 85°E, 102°E, 115°E could reflect the three major ladders of China. In the vertical direction, the RDLS increases with the increase of altitude. Analysis of the correlation between RDLS and population distribution in China and its regional difference shows that the R 2 value between RDLS and population density is 0.91 and RDLS is an important factor influencing the spatial distribution of population. More than 85% of the people in China live in areas where the RDLS is less than one (1), while the population in areas with RDLS greater than 3 accounts only for 0.57% of the total. The regional difference of correlation between RDLS and population within China is significant and such correlation is significant in Central China and South China and weak in Inner Mongolia and Tibet.
With the degeneration of environment and acceleration of urbanization, human environment has attracted great attention worldwide. This paper sets up the Human Settlements Environment Index (HEI) model and evaluates the natural environment suitability for Human Settlements in China based on GIS technology. The results show that the HEI of China decreases from southeast to northwest in general, HEI is significantly correlated with population density at grid size and the correlation coefficient (r) between them reaches 0.93, which indicates that natural environment suitability for Human Settlements has a significant influence on population distribution. Most people in China mainly concentrate in areas with high natural environment suitability. The total suitable area is 430.47×10 4 km 2 , which accounts for nearly 45% of the total land area in China, while the proportion of people living in the area reaches 96.56%. With a population density of 18 people per square kilometer, the critical area is the transitional region for people to live in China. The critical area covers 225.11×10 4 km 2 with a population of 41.12 million. The non-suitable area covers 304.42×10 4 km 2 with a population of only 2.49 million.
Simultaneous IFVA and ICGA are generally safe procedures with an acceptable incidence of an adverse reaction. However, patients with drug allergy history may have a higher incidence and greater severity of an adverse reaction.
2,4-Diacetylphloroglucinol hydrolase PhlG from Pseudomonas fluorescens catalyzes hydrolytic carbon-carbon (C-C) bond cleavage of the antibiotic 2,4-diacetylphloroglucinol to form monoacetylphloroglucinol, a rare class of reactions in chemistry and biochemistry. To investigate the catalytic mechanism of this enzyme, we determined the three-dimensional structure of PhlG at 2.0 Å resolution using x-ray crystallography and MAD methods. The overall structure includes a small N-terminal domain mainly involved in dimerization and a C-terminal domain of Bet v1-like fold, which distinguishes PhlG from the classical ␣/-fold hydrolases. A dumbbell-shaped substrate access tunnel was identified to connect a narrow interior amphiphilic pocket to the exterior solvent. The tunnel is likely to undergo a significant conformational change upon substrate binding to the active site. Structural analysis coupled with computational docking studies, site-directed mutagenesis, and enzyme activity analysis revealed that cleavage of the 2,4-diacetylphloroglucinol C-C bond proceeds via nucleophilic attack by a water molecule, which is coordinated by a zinc ion. In addition, residues Tyr 121 , Tyr 229 , and Asn 132 , which are predicted to be hydrogen-bonded to the hydroxyl groups and unhydrolyzed acetyl group, can finely tune and position the bound substrate in a reactive orientation. Taken together, these results revealed the active sites and zinc-dependent hydrolytic mechanism of PhlG and explained its substrate specificity as well.
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