The oxidative dehydrogenation (ODH) of propane on single-crystal V(2)O(5)(001) is studied by periodic density functional theory (DFT) calculations. The energetics and pathways for the propane to propene conversion are determined. We show that (i) the C-H bond of propane can be activated by both the terminal and the bridging lattice O atoms on the surface with similar activation energies. At the terminal O site both the radical and the oxo-insertion pathways are likely for the C-H bond activation, while only the oxo-insertion mechanism is feasible at the bridging O site. (ii) Compared to that at the terminal O site, the propene production from the propoxide at the bridging O site is much easier due to the weaker binding of propoxide at the bridging O. It is concluded that single-crystal V(2)O(5)(001) is not a good catalyst due to the terminal O being too active to release propene. It is expected that an efficient catalyst for the ODH reaction has to make a compromise between the ability to activate the C-H bond and the ability to release propene.

Summary Asymmetric cell division requires the establishment of cortical cell polarity and the orientation of the mitotic spindle along the axis of cell polarity. Evidence from invertebrates demonstrates that the Par3/Par6/aPKC and NuMA/LGN/Gαi complexes, which are thought to be physically linked by the adapter protein mInscuteable (mInsc), play indispensable roles in this process. However, the molecular basis for the binding of LGN to NuMA and mInsc is poorly understood. The high resolution structures of the LGN/NuMA and LGN/mInsc complexes presented here provide mechanistic insights into the distinct and highly specific interactions of the LGN TPR repeats with mInsc and NuMA. Structural comparisons, together with biochemical and cell biology studies, demonstrate that the interactions of NuMA and mInsc with LGN are mutually exclusive, with mInsc binding preferentially. Our results suggest that the Par3/mInsc/LGN and NuMA/LGN/Gαi complexes play sequential and partially overlapping roles in asymmetric cell division.

Membrane-associated guanylate kinases (MAGUKs) are a large family of scaffold proteins that play essential roles in tissue developments, cell-cell communications, cell polarity control, and cellular signal transductions. Despite extensive studies over the past two decades, the functions of the signature guanylate kinase domain (GK) of MAGUKs are poorly understood. Here we show that the GK domain of DLG1/SAP97 binds to asymmetric cell division regulatory protein LGN in a phosphorylation-dependent manner. The structure of the DLG1 SH3-GK tandem in complex with a phospho-LGN peptide reveals that the GMP-binding site of GK has evolved into a specific pSer/ pThr-binding pocket. Residues both N-and C-terminal to the pSer are also critical for the specific binding of the phospho-LGN peptide to GK. We further demonstrate that the previously reported GK domain-mediated interactions of DLGs with other targets, such as GKAP/DLGAP1/ SAPAP1 and SPAR, are also phosphorylation dependent. Finally, we provide evidence that other MAGUK GKs also function as phospho-peptide-binding modules. The discovery of the phosphorylation-dependent MAGUK GK/ target interactions indicates that MAGUK scaffoldmediated signalling complex organizations are dynamically regulated.

Twenty-three density functional theory (DFT) methods, including the second- and the third-generation functionals, are tested in conjunction with two basis sets (LANL2DZ and SDD) for studying the properties of neutral and ionic silver clusters. We find that DFT methods incorporating the uniform electron gas limit in the correlation functional, namely, those with Perdew's correlation functionals (PW91, PBE, P86, and TPSS), Becke's B95, and the Van Voorhis-Scuseria functional VSXC, generally perform better than the other group of functionals, e.g., those incorporating the LYP correlation functional and variations of the B97 functional. Strikingly, these two groups of functionals can produce qualitatively different results for the Ag3 and Ag4 clusters. The energetic properties and vibrational frequencies of Ag(n) are also evaluated by the different functionals. The present study shows that the choice of DFT methods for heavy metals may be critical. It is found that the exact-exchange-incorporated PBE functional (PBE1PBE) is among the best for predicting the range of properties.

The study of the reactions of transition metal atoms with water is continued in this work. Here we report the study of the reactions of Fe with H2O and FeO with H2. In agreement with previous thermal atom experiments, laser-ablated Fe atoms reacted with H2O to form the FeOH2 and HFeOH molecules as characterized by matrix isolation FTIR spectroscopy. On photolysis, the Fe atoms could further insert into the OH bonds in H2O molecules with a stepwise pattern to form multi metal−oxo core species including HFeOFeH, HFeOFeOH, and possibly HFeOFeOFeH, which were identified by isotopic substitutions and density functional calculations. Reactions of FeO with H2 also lead to HFeOH as the primary product. In addition, a potential energy surface for the Fe + H2O ⇔ FeO + H2 reaction was constructed to elucidate the reaction mechanisms.

Transduction of biological signals from receptors at the plasma membrane to their targets in cytoplasm and nucleus relies on specific protein-protein interactions. A common strategy used by cells is to organize proteins in the same signaling cascade into large molecular weight, multiprotein complexes. PDZ domain proteins have been shown to play important roles in assembling various signaling complexes. Here, we first present biophysical basis of the advantages of organizing proteins in a signaling cascade into a clustered multiprotein complex. We then discuss the structure, ligand binding, and function of PDZ domains in organizing synaptic signaling complexes.

Oxidative dehydrogenation (ODH) of ethane over the V 2 O 5 (001) surface has been carried out using periodic density functional theory (DFT) calculations. We show that the first C-H bond activation leading to an ethoxide intermediate is the rate-limiting step of the reaction. The most feasible pathway for the C-H bond activation is predicted to take place at the O(1) (VdO) site, with activation energy of 35.1 kcal/mol. The O(2) (V-O-V) site is less active for C-H bond activation, with an energy barrier of 37.6 kcal/mol. However, the O(1) site exhibits much lower selectivity to ethene formation than O(2) because the side reaction leading to acetaldehyde occurs more easily than ethene production on O(1), whereas O(2) is inert for acetaldehyde formation. On the basis of our results, the ODH reactions of ethane and propane are systematically compared and discussed.

ATP binding cassette transporters are integral membrane proteins that use the energy released from ATP hydrolysis at the two nucleotide binding domains (NBDs) to translocate a wide variety of substrates through a channel at the two transmembrane domains (TMDs) across the cell membranes. MsbA from Gram-negative bacteria is a lipid and multidrug resistance ATP binding cassette exporter that can undergo large scale conformational changes between the outward-facing and the inwardfacing conformations revealed by crystal structures in different states. Here, we use targeted molecular dynamics simulation methods to explore the atomic details of the conformational transition from the outward-facing to the inward-facing states of MsbA. The molecular dynamics trajectories revealed a clear spatiotemporal order of the conformational movements. The disruption of the nucleotide binding sites at the NBD dimer interface is the very first event that initiates the following conformational changes, verifying the assumption that the conformational conversion is triggered by ATP hydrolysis. The conserved x-loops of the NBDs were identified to participate in the interaction network that stabilizes the cytoplasmic tetrahelix bundle of the TMDs and play an important role in mediating the cross-talk between the NBD and TMD. The movement of the NBD dimer is transmitted through x-loops to break the tetrahelix bundle, inducing the packing rearrangements of the transmembrane helices at the cytoplasmic side and the periplasmic side sequentially. The packing rearrangement within each periplasmic wing of TMD that results in exposure of the substrate binding sites occurred at the end stage of the trajectory, preventing the wrong timing of the binding site accessibility. ATP binding cassette (ABC)2 transporters are integral membrane proteins that utilize the energy of ATP hydrolysis to translocate a wide variety of substrates, including ions, peptides, sugars, toxins, lipids, and drug molecules, across the cell membrane (1, 2). ABC transporters are implicated in multidrug resistance (MDR) and represent key targets for drug development (3, 4). They are minimally composed of two transmembrane (TM) domains (TMDs) and a pair of nucleotide-binding domains (NBDs) (5-7). TMDs usually enclose a central pore, which probably acts as the translocation pathway of substrates. Despite various architectures of the central pore demonstrated in the crystal structures of different ABC transporters reported so far, most of them can be classified into two states, i.e. the inward-facing (8 -13) and the outward-facing states (14 -16). The inward-facing conformation allows access of the pore to the cytoplasm but not to the periplasm and vice versa for the outward-facing conformation. Large scale conformational changes between these two states were proposed to be essential for the transport cycle (17-19). The NBDs are highly conserved among ABC transporter families containing conserved structural motifs such as Walker A (P loop) and LSGGQ (signature) motifs. The two NB...