Diverse Levels of Sequence Selectivity and Catalytic Efficiency of Protein-Tyrosine Phosphatases

The sequence selectivity of 14 classical protein-tyrosine phosphatases (PTPs) (PTPRA, PTPRB, PTPRC, PTPRD, PTPRO, PTP1B, SHP-1, SHP-2, HePTP, PTP-PEST, TCPTP, PTPH1, PTPD1, and PTPD2) was systematically profiled by screening their catalytic domains against combinatorial peptide libraries. All of the PTPs exhibit similar preference for pY peptides rich in acidic amino acids and disfavor positively charged sequences, but differ vastly in their degrees of preference/disfavor. Some PTPs (PTP-PEST, SHP-1, and SHP-2) are highly selective for acidic over basic (or neutral) peptides (by >105-fold), whereas others (PTPRA and PTPRD) show no to little sequence selectivity. PTPs also have diverse intrinsic catalytic efficiencies (kcat/KM values against optimal substrates), which differ by >105-fold due to different kcat and/or KM values. Moreover, PTPs show little positional preference for the acidic residues relative to the pY residue. Mutation of Arg47 of PTP1B, which is located near the pY-1 and pY-2 residues of a bound substrate, decreased the enzymatic activity by 3–18-fold toward all pY substrates containing acidic residues anywhere within the pY-6 to pY+5 region. Similarly, mutation of Arg24, which is situated near the C-terminus of a bound substrate, adversely affected the kinetic activity of all acidic substrates. A co-crystal structure of PTP1B bound with a nephrin pY1193 peptide suggests that Arg24 engages in electrostatic interactions with acidic residues at the pY+1, pY+2, and likely other positions. These results suggest that long-range electrostatic interactions between positively charged residues near the PTP active site and acidic residues on pY substrates allow a PTP to bind acidic substrates with similar affinities and the varying levels of preference for acidic sequences by different PTPs are likely caused by the different electrostatic potentials near their active sites. The implications of the varying sequence selectivity and intrinsic catalytic activities with respect to PTP in vivo substrate specificity and biological functions are discussed

Global weak solutions for the compressible active liquid crystal system

We study the hydrodynamics of compressible flows of active liquid crystals in the Beris--Edwards hydrodynamics framework, using the Landau--de Gennes $Q$-tensor order parameter to describe liquid crystalline ordering. We prove the existence of global weak solutions for this active system in three space dimensions by the three-level approximations and weak convergence argument. New techniques and estimates are developed to overcome the difficulties caused by the active terms

Global solutions to the three-dimensional full compressible magnetohydrodynamic flows

The equations of the three-dimensional viscous, compressible, and heat conducting magnetohydrodynamic flows are considered in a bounded domain. The viscosity coefficients and heat conductivity can depend on the temperature. A solution to the initial-boundary value problem is constructed through an approximation scheme and a weak convergence method. The existence of a global variational weak solution to the three-dimensional full magnetohydrodynamic equations with large data is established

Global Existence and Large-Time Behavior of Solutions to the Three-Dimensional Equations of Compressible Magnetohydrodynamic Flows

The three-dimensional equations of compressible magnetohydrodynamic isentropic flows are considered. An initial-boundary value problem is studied in a bounded domain with large data. The existence and large-time behavior of global weak solutions are established through a three-level approximation, energy estimates, and weak convergence for the adiabatic exponent $\gamma>\frac32$ and constant viscosity coefficients

Isometric Immersions and Compensated Compactness

A fundamental problem in differential geometry is to characterize intrinsic metrics on a two-dimensional Riemannian manifold ${\mathcal M}^2$ which can be realized as isometric immersions into $\R^3$. This problem can be formulated as initial and/or boundary value problems for a system of nonlinear partial differential equations of mixed elliptic-hyperbolic type whose mathematical theory is largely incomplete. In this paper, we develop a general approach, which combines a fluid dynamic formulation of balance laws for the Gauss-Codazzi system with a compensated compactness framework, to deal with the initial and/or boundary value problems for isometric immersions in $\R^3$. The compensated compactness framework formed here is a natural formulation to ensure the weak continuity of the Gauss-Codazzi system for approximate solutions, which yields the isometric realization of two-dimensional surfaces in $\R^3$. As a first application of this approach, we study the isometric immersion problem for two-dimensional Riemannian manifolds with strictly negative Gauss curvature. We prove that there exists a $C^{1,1}$ isometric immersion of the two-dimensional manifold in $\R^3$ satisfying our prescribed initial conditions. TComment: 25 pages, 6 figue

Identification of a Key Amino Acid of LuxS Involved in AI-2 Production in Campylobacter jejuni

Autoinducer-2 (AI-2) mediated quorum sensing has been associated with the expression of virulence factors in a number of pathogenic organisms and has been demonstrated to play a role in motility and cytolethal distending toxin (cdt) production in Campylobacter jejuni. We have initiated the work to determine the molecular basis of AI-2 synthesis and the biological functions of quorum sensing in C. jejuni. In this work, two naturally occurring variants of C. jejuni 81116 were identified, one producing high-levels of AI-2 while the other is defective in AI-2 synthesis. Sequence analysis revealed a G92D mutation in the luxS gene of the defective variant. Complementation of the AI-2− variant with a plasmid encoded copy of the wild-type luxS gene or reversion of the G92D mutation by site-directed mutagenesis fully restored AI-2 production by the variant. These results indicate that the G92D mutation alone is responsible for the loss of AI-2 activity in C. jejuni. Kinetic analyses showed that the G92D LuxS has a ∼100-fold reduced catalytic activity relative to the wild-type enzyme. Findings from this study identify a previously undescribed amino acid that is essential for AI-2 production by LuxS and provide a unique isogenic pair of naturally occurring variants for us to dissect the functions of AI-2 mediated quorum sensing in Campylobacter

High-temperature steam reforming of bio-oil derived light organics and methane to hydrogen-rich gas with trace CO via rational temperature control

Steam reforming of methane or bio-oil is generally performed at high temperatures (>600 °C) to maintain the efficiency of the process. One main disadvantage of steam reforming at that high temperature is the formation of a large amount of CO due to the predomination of the reverse water gas shift reaction and the reformate gas with this level of CO cannot feed fuel cells. In this study a reactor with constant and decreasing temperature zones is developed to produce hydrogen-rich gas with trace CO from bio-oil derived light organics and methane. In the constant-temperature zone, the high temperature employed effectively promotes the reforming of organics and suppresses the generation of both complex organic by-products and coke. In the decreasing temperature zone, the CO produced in the constant-temperature zone is stepwisely and efficiently reduced to a ppm level using steam. In addition, the coke distribution along the catalyst bed varied a lot in the constant-temperature zone and the decreasing temperature zone, due to the different reaction network in the different temperature ranges. Via rational reaction temperature control, the efficient reforming of methane and the bio-oil derived light organics and the simultaneous elimination of CO is successfully achieved in one step in one reactor