Structural characterization of angiotensin I-converting enzyme in complex with a selenium analogue of captopril

Human somatic angiotensin I-converting enzyme (ACE), a zinc-dependent dipeptidyl carboxypeptidase, is central to the regulation of the renin-angiotensin aldosterone system. It is a well-known target for combating hypertension and related cardiovascular diseases. In a recent study by Bhuyan and Mugesh [Org. Biomol. Chem. (2011) 9, 1356-1365], it was shown that the selenium analogues of captopril (a well-known clinical inhibitor of ACE) not only inhibit ACE, but also protect against peroxynitrite-mediated nitration of peptides and proteins. Here, we report the crystal structures of human testis ACE (tACE) and a homologue of ACE, known as AnCE, from Drosophila melanogaster in complex with the most promising selenium analogue of captopril (SeCap) determined at 2.4 and 2.35 angstrom resolution, respectively. The inhibitor binds at the active site of tACE and AnCE in an analogous fashion to that observed for captopril and provide the first examples of a protein-selenolate interaction. These new structures of tACE-SeCap and AnCE-SeCap inhibitor complexes presented here provide important information for further exploration of zinc coordinating selenium-based ACE inhibitor pharmacophores with significant antioxidant activity.

Microwave spectrum and structure of C(6)H(5)CCH center dot center dot center dot H(2)S complex

Rotational spectra of C(6)H(5)CCH center dot center dot center dot H(2)S, C(6)H(5)CCH center dot center dot center dot H(2)(34)S, C(6)H(5)CCH center dot center dot center dot HDS, C(6)H(5)CCH center dot center dot center dot D(2)S and C(6) H(5)CCD center dot center dot center dot H(2)S complexes have been observed using a pulsed nozzle Fourier transform microwave spectrometer. The observed spectrum is consistent with a structure in which hydrogen sulfide is located over the phenyl ring pi cloud and the distance between the centers of masses of the two monomers is 3.74 +/- 0.01 angstrom. In the complex, the H(2)S unit is shifted from the phenyl ring center towards the acetylene group. The vibrationally averaged structure has an effective Cs symmetry. Ab initio calculations were performed at MP2/aug-cc-pVDZ level of theory to locate the possible geometries of the complex. The calculations reveal the experimentally observed structure to be more stable than a coplanar arrangement of the monomers, which was observed for the C(6)H(5)CCH center dot center dot center dot H(2)O complex. Atoms in molecule theoretical analysis shows the presence of S-H center dot center dot center dot pi hydrogen bond. For the parent isotopologue, each transition frequency was found to split into two resulting from an interchange of the equivalent hydrogens of H(2)S unit in the complex. (C) 2011 Elsevier Inc. All rights reserved.

Spin State Selective Excitation of Single Quantum Transitions Using Multiple Quantum Spectroscopy- an Aid to Analyse Complex Proton NMR spectra of Oriented Molecules

NMR spectra of molecules oriented in liquid-crystalline matrix provide information on the structure and orientation of the molecules. Thermotropic liquid crystals used as an orienting media result in the spectra of spins that are generally strongly coupled. The number of allowed transitions increases rapidly with the increase in the number of interacting spins. Furthermore, the number of single quantum transitions required for analysis is highly redundant. In the present study, we have demonstrated that it is possible to separate the subspectra of a homonuclear dipolar coupled spin system on the basis of the spin states of the coupled heteronuclei by multiple quantum (MQ)−single quantum (SQ) correlation experiments. This significantly reduces the number of redundant transitions, thereby simplifying the analysis of the complex spectrum. The methodology has been demonstrated on the doubly 13C labeled acetonitrile aligned in the liquid-crystal matrix and has been applied to analyze the complex spectrum of an oriented six spin system.

On the Production of Anorexic Plan Diagrams

A "plan diagram" is a pictorial enumeration of the execution plan choices of a database query optimizer over the relational selectivity space. We have shown recently that, for industrial-strength database engines, these diagrams are often remarkably complex and dense, with a large number of plans covering the space. However, they can often be reduced to much simpler pictures, featuring significantly fewer plans, without materially affecting the query processing quality. Plan reduction has useful implications for the design and usage of query optimizers, including quantifying redundancy in the plan search space, enhancing useability of parametric query optimization, identifying error-resistant and least-expected-cost plans, and minimizing the overheads of multi-plan approaches. We investigate here the plan reduction issue from theoretical, statistical and empirical perspectives. Our analysis shows that optimal plan reduction, w.r.t. minimizing the number of plans, is an NP-hard problem in general, and remains so even for a storage-constrained variant. We then present a greedy reduction algorithm with tight and optimal performance guarantees, whose complexity scales linearly with the number of plans in the diagram for a given resolution. Next, we devise fast estimators for locating the best tradeoff between the reduction in plan cardinality and the impact on query processing quality. Finally, extensive experimentation with a suite of multi-dimensional TPCH-based query templates on industrial-strength optimizers demonstrates that complex plan diagrams easily reduce to "anorexic" (small absolute number of plans) levels incurring only marginal increases in the estimated query processing costs.

A homobimetallic complex of chromium(0) with a sigma-borane component

The synthesis, characterization, and reactivity of a chromium(0) complex bearing an amine-borane moiety (eta(6)-C(6)H(5)CH(2)NMe(2)center dot BH(3))Cr(CO)(3) (2) is reported. Photolysis of complex 2 results in the elimination of a CO ligand followed by the formation of an intramolecular sigma-borane complex (eta(1)-(eta(6)- C(6)H(5)CH(2)NMe(2)center dot BH(2)-H))Cr(CO)(2) (3). This species was characterized in solution by NMR spectroscopy. Reaction of complex 2 with photochemically generated (OC)(5)Cr(THF) affords a novel homobimetallic sigma-borane complex (OC)(3)Cr(eta(6)-C(6)H(5)CH(2)NMe(2)center dot BH(2)-H-Cr(CO)(5)) (4), wherein one of the BH moieties is bound to the chromium center in an eta(1)-fashion. The sigma-borane complex 4 was isolated in moderate to good yield (72%). The BH(3) fragment in the complexes 3 and 4 are highly dynamic involving exchange of the BH hydrogen bound to the metal with the terminal BH hydrogen atoms. The dynamics has been studied using variable-temperature NMR spectroscopy. Complexes 2 and 4 have been characterized by X-ray crystallography.

Spectral Finite Element Modeling of Complex Structures for Applications in Real-time Structural Health Monitoring

In this paper we discuss the recent progresses in spectral finite element modeling of complex structures and its application in real-time structural health monitoring system based on sensor-actuator network and near real-time computation of Damage Force Indicator (DFI) vector. A waveguide network formalism is developed by mapping the original variational problem into the variational problem involving product spaces of 1D waveguides. Numerical convergence is studied using a h()-refinement scheme, where is the wavelength of interest. Computational issues towards successful implementation of this method with SHM system are discussed.

Structure of the Pyridine-Chloranil Complex in Solution: A Surprise from Depolarized Hyper-Rayleigh Scattering Measurements

In this article, we report the structure of a 1:1 charge transfer complex between pyridine (PYR) and chloranil (CHL) in solution (CHCl(3)) from the measurement of hyperpolarizability (beta(HRS)) and linear and circular depolarization ratios, D and D', respectively, by the hyper-Rayleigh scattering technique and state-of-the-art quantum chemical calculations. Using linearly (electric field vector along X) and circularly polarized incident light, respectively, we have measured two macroscopic depolarization ratios D = I(X,X)(2 omega)/I(X,Z)(2 omega) and D' = I(X,C)(2 omega)/I(Z,C)(2 omega) in the laboratory fixed XYZ frame by detecting the second harmonic (SH) scattered light in a polarization resolved fashion. The stabilization energy and the optical gap calculated through the MP2/cc-pVDZ method using Gaussian09 were not significantly different to distinguish between the cofacial and T-shape structures. Only when the experimentally obtained beta(HRS) and the depolarization ratios, D and D', were matched with the theoretically computed values from single and double configuration interaction (SDCI) calculations performed using the ZINDO-SCRF technique, we concluded that the room temperature equilibrium structure of the complex is cofacial. This is in sharp contrast to an earlier theoretical prediction of the T-shape structure of the complex.

Subdiffusion as a model of transport through the nuclear pore complex

Cargo transport through the nuclear pore complex continues to be a subject of considerable interest to experimentalists and theorists alike. Several recent studies have revealed details of the process that have still to be fully understood, among them the apparent nonlinearity between cargo size and the pore crossing time, the skewed, asymmetric nature of the distribution of such crossing times, and the non-exponentiality in the decay profile of the dynamic autocorrelation function of cargo positions. In this paper, we show that a model of pore transport based on subdiffusive particle motion is in qualitative agreement with many of these observations. The model corresponds to a process of stochastic binding and release of the particle as it moves through the channel. It suggests that the phenylalanine-glycine repeat units that form an entangled polymer mesh across the channel may be involved in translocation, since these units have the potential to intermittently bind to hydrophobic receptor sites on the transporter protein. (C) 2011 American Institute of Physics. [doi:10.1063/1.3651100]

Distributed Simulation Of Flexible Manufacturing Systems

Flexible Manufacturing Systems (FMS), widely considered as the manufacturing technology of the future, are gaining increasing importance due to the immense advantages they provide in terms of cost, quality and productivity over the conventional manufacturing. An FMS is a complex interconnection of capital intensive resources and high levels of system performance is very crucial for survival in a competing environment.Discrete event simulation is one of the most popular methods for performance evaluation of FMS during planning, design and operation phases. Indeed fast simulators are suggested for selection of optimal strategies for flow control (which part type to enter and at what instant), AGV scheduling (which vehicle to carry which part), routing (which machine to process the part) and part selection (which part for processing next). In this paper we develop a C-net based model for an FMS and use the same for distributed discrete event simulation. We illustrate using examples the efficacy of destributed discrete event simulation for the performance evaluation of FMSs.

Multiple garnet growth in garnet-kyanite-staurolite gneiss, Pangong metamorphic complex, Ladakh Himalaya: New constraints on tectonic setting

Garnet-kyanite-staurolite gneiss in the Pangong complex, Ladakh Himalaya, contains porphyroblastic euhedral garnets, blades of kyanite and resorbed staurolite surrounded by a fine-grained muscovite-biotite matrix associated with a leucogranite layer. Sillimanite is absent. The gneiss contains two generations of garnet in cores and rims that represent two stages of metamorphism. Garnet cores are extremely rich in Mn (X(Sps) = 0.35-038) and poor in Fe (X(Alm) = 0.40-0.45), whereas rims are relatively Mn-poor (X(Sps) =0.07-0.08), and rich in Fe (X(Alm), = 0.75-0.77). We suggest that garnet cores formed during prograde metamorphism in a subduction zone followed by abrupt exhumation, during early collision of the Ladakh arc and Karakoram block. The subsequent India-Asia continental collision subducted the metamorphic rocks to a mid-crustal level, where the garnet rims overgrew the Mn-rich cores at ca. 680 degrees C and ca. 8.5 kbar. PT calculations were estimated from phase diagrams calculated using a calculated bulk chemical composition in the Mn-NCKFMASHT system for the garnet-kyanite-staurolite-bearing assemblage. Muscovites from the metamorphic rocks and associated leucogranites have consistent K-Ar ages (ca. 10 Ma), closely related to activation of the Karakoram fault in the Pangong metamorphic complex. These ages indicate the contemporaneity of the exhumation of the metamorphic rocks and the cooling of the leucogranites. (C) 2011 Elsevier B.V. All rights reserved.