Toward the three-dimensional structure and lysophosphatidic acid binding characteristics of the LPA4/p2y9/GPR23 receptor: A homology modeling study

Lysophosphatidic acid (LPA) is a naturally occurring phospholipid that initiates a broad array of biological processes, including those involved in cell proliferation, survival and migration via activation of specific G protein-coupled receptors located on the cell surface. To date, at least five receptor subtypes (LPA_1–5) have been identified. The LPA_1–3 receptors are members of the endothelial cell differentiation gene (Edg) family. LPA₄, a member of the purinergic receptor family, and the recently identified LPA₅ are structurally distant from the canonical Edg LPA_1–3 receptors. LPA₄ and LPA₅ are linked to G_q, G_12/13 and G_s but not G_i, while LPA_1–3 all couple to G_i in addition to G_q and G_12/13. There is also evidence that LPA₄ and LPA₅ are functionally different from the Edg LPA receptors. Computational modeling has provided useful information on the structure–activity relationship (SAR) of the Edg LPA receptors. In this work, we focus on the initial analysis of the structural and ligand-binding properties of LPA₄, a prototype non-Edg LPA receptor. Three homology models of the LPA₄ receptor were developed based on the X-ray crystal structures of the ground state and photoactivated bovine rhodopsin and the recently determined human β₂-adrenergic receptor. Docking studies of LPA in the homology models were then conducted, and plausible LPA binding loci were explored. Based on these analyses, LPA is predicted to bind to LPA₄ in an orientation similar to that reported for LPA_1–3, but through a different network of hydrogen bonds. In LPA_1–3, the ligand polar head group is reported to interact with residues at positions 3.28, 3.29 and 7.36, whereas three non-conserved amino acid residues, S114(3.28), T187(EL2) and Y265(6.51), are predicted to interact with the polar head group in the LPA₄ receptor models.     

Characterization of ozone sensors based on WO3 reactively sputtered films: influence of O2 concentration in the sputtering gas, and working temperature

We report on electrical responses of tungsten oxide thin film ozone sensors based on a tungsten trioxide (WO₃)/tin oxide (SiO₂)/Si structure with interdigitated Pt electrodes. The influence of O₂ concentration in the sputtering gas and working temperature of the sensor are investigated. Sensitivity to ozone increases with O₂ content in the sputtering gas. It reaches its highest value for sensors fabricated with 50% O₂. For these sensors, the best ozone sensitivity and shortest response and recovery times are obtained at a working temperature of 523 K. Ozone sensitivity is compared to other ozone sensors.     

Homology modeling of a Class A GPCR in the inactive conformation: A quantitative analysis of the correlation between model/template sequence identity and model accuracy

With the present work we quantitatively studied the modellability of the inactive state of Class A G protein-coupled receptors (GPCRs). Specifically, we constructed models of one of the Class A GPCRs for which structures solved in the inactive state are available, namely the β₂ AR, using as templates each of the other class members for which structures solved in the inactive state are also available. Our results showed a detectable linear correlation between model accuracy and model/template sequence identity. This suggests that the likely accuracy of the homology models that can be built for a given receptor can be generally forecasted on the basis of the available templates. We also probed whether sequence alignments that allow for the presence of gaps within the transmembrane domains to account for structural irregularities afford better models than the classical alignment procedures that do not allow for the presence of gaps within such domains. As our results indicated, although the overall differences are very subtle, the inclusion of internal gaps within the transmembrane domains has a noticeable a beneficial effect on the local structural accuracy of the domain in question.