bluuebunny/crossref_metadata_2025 huggingface dataset:
Single‐stranded DNA binding of the cold‐shock protein CspB from Bacillus subtilis: NMR mapping and mutational characterization
Authors: Zeeb Markus , Balbach Jochen
Published: August 2003

Cold‐shock proteins (CSPs) bind to single‐stranded nucleic acids, thereby acting as a “RNA chaperone.” To gain deeper insights into the rather unspecific nature of ssDNA/RNA binding, we characterized the binding interface of CspB from Bacillus subtilis to a 25‐mer of ssDNA (Y‐Box25) using heteronuclear 2D NMR spectroscopy. Seventeen residues, including eight out of nine aromatic amino acids, are directly involved in the Y‐Box25 interaction and were identified by extreme line broadening of their cross‐peaks. Eight residues belong to the earlier proposed RNP binding motifs. A second set of seven backbone amides becomes evident by major chemical shift perturbations reporting remote conformational rearrangements upon binding. These residues are located in loop β3–β4 and loopβ4–β5, and include Ile18. The individual contributions of the so‐identified residues were examined by fluorescence titration experiments of 15 CspB variants. Phenylalanine substitutions in‐ and outside the RNP motifs significantly reduce the binding affinity. Unrestricted possible backbone conformations of loop β3–β4 also markedly contribute to binding. Stopped‐flow fluorescence kinetics revealed that the different binding affinities of CspB variants are determined by the dissociation rate, whereas the association rate remains unchanged. This might be of importance for the “RNA chaperone” activity of CspB.
Comparison of β‐lactamases of classes A and D: 1.5‐Å crystallographic structure of the class D OXA‐1 oxacillinase
Authors: Sun Tao , Nukaga Michiyoshi , Mayama Kayoko , Braswell Emory H. , Knox James R.
Published: August 2003

The crystallographic structure of the Escherichia coli OXA‐1 β‐lactamase has been established at 1.5‐Å resolution and refined to R = 0.18. The 28.2‐kD oxacillinase is a class D serine β‐lactamase that is especially active against the penicillin‐type β‐lactams oxacillin and cloxacillin. In contrast to the structures of OXA‐2, OXA‐10, and OXA‐13 belonging to other subclasses, the OXA‐1 molecule is monomeric rather than dimeric and represents the subclass characterized by an enlarged Ω loop near the β‐lactam binding site. The 6‐residue hydrophilic insertion in this loop cannot interact directly with substrates and, instead, projects into solvent. In this structure at pH 7.5, carboxylation of the conserved Lys 70 in the catalytic site is observed. One oxygen atom of the carboxylate group is hydrogen bonded to Ser 120 and Trp 160. The other oxygen atom is more exposed and hydrogen bonded to the Oγ of the reactive Ser 67. In the overlay of the class D and class A binding sites, the carboxylate group is displaced ca. 2.6 Å from the carboxylate group of Glu 166 of class A enzymes. However, each group is equidistant from the site of the water molecule expected to function in hydrolysis, and which could be activated by the carboxylate group of Lys 70. In this ligand‐free OXA‐1 structure, no water molecule is seen in this site, so the water molecule must enter after formation of the acyl‐Ser 67 intermediate.
Protein hydrogen exchange mechanism: Local fluctuations
Authors: Maity Haripada , Lim Woon Ki , Rumbley Jon N. , Englander S. Walter
Published: August 2003

Experiments were done to study the dynamic structural motions that determine protein hydrogen exchange (HX) behavior. The replacement of a solvent‐exposed lysine residue with glycine (Lys8Gly) in a helix of recombinant cytochrome c does not perturb the native structure, but it entropically potentiates main‐chain flexibility and thus can promote local distortional motions and large‐scale unfolding. The mutation accelerates amide hydrogen exchange of the mutated residue by about 50‐fold, neighboring residues in the same helix by less, and residues elsewhere in the protein not at all, except for Leu98, which registers the change in global stability. The pattern of HX changes shows that the coupled structural distortions that dominate exchange can be several residues in extent, but they expose to exchange only one amide NH at a time. This ‘local fluctuation’ mode of hydrogen exchange may be generally recognized by disparate near‐neighbor rates and a low dependence on destabilants (denaturant, temperature, pressure). In contrast, concerted unfolding reactions expose multiple neighboring amide NHs with very similar computed protection factors, and they show marked destabilant sensitivity. In both modes, ionic hydrogen exchange catalysts attack from the bulk solvent without diffusing through the protein matrix.
Induced fit in guanidino kinases—comparison of substrate‐free and transition state analog structures of arginine kinase
Authors: Yousef Mohammad S. , Clark Shawn A. , Pruett Pamela K. , Somasundaram Thayumanasamy , Ellington W. Ross , Chapman Michael S.
Published: August 2003

Arginine kinase (AK) is a member of the guanidino kinase family that plays an important role in buffering ATP concentration in cells with high and fluctuating energy demands. The AK specifically catalyzes the reversible phosphoryl transfer between ATP and arginine. We have determined the crystal structure of AK from the horseshoe crab (Limulus polyphemus) in its open (substrate‐free) form. The final model has been refined at 2.35 Å with a final R of 22.3% (Rfree = 23.7%). The structure of the open form is compared to the previously determined structure of the transition state analog complex in the closed form. Classically, the protein would be considered two domain, but dynamic domain (DynDom) analysis shows that most of the differences between the two structures can be considered as the motion between four rigid groups of nonsequential residues. ATP binds near a cluster of positively charged residues of a fixed dynamic domain. The other three dynamic domains close the active site with separate hinge rotations relative to the fixed domain. Several residues of key importance for the induced motion are conserved within the phosphagen kinase family, including creatine kinase. Substantial conformational changes are induced in different parts of the enzyme as intimate interactions are formed with both substrates. Thus, although induced fit occurs in a number of phosphoryl transfer enzymes, the conformational changes in phosphagen kinases appear to be more complicated than in prior examples.
Electrostatic interactions in the reconstitution of an SH2 domain from constituent peptide fragments
Authors: Ojennus Deanna Dahlke , Lehto Sarah E. , Wuttke Deborah S.
Published: August 2003

Fragment complementation has been used to delineate the essential recognition elements for stable folding in Src homology 2 (SH2) domains by using NMR spectroscopy, alanine scanning, and surface plasmon resonance. The unfolded 9‐kD and 5‐kD peptide fragments formed by limited proteolytic digestion of the N‐terminal SH2 domain from the p85α subunit of phosphatidylinositol 3′‐kinase fold into an active native‐like structure on interaction with one another. The corresponding 5‐kD fragment of the homologous Src protein, however, was not capable of structurally complementing the p85 9‐kD fragment, indicating that fragment complementation among these SH2 domains is sensitive to the sequence differences between the Src and p85 domains. Partial complementation and folding activity could be recovered with hybrid sequences of these SH2 domains. Complete alanine scanning of the 5‐kD p85 fragment was used to identify the sequence recognition elements required for complex formation. The alanine substitutions in the p85 5‐kD fragment that abolished binding affinity with the cognate 9‐kD fragment correlate well with highly conserved residues among SH2 domains that are either integrally involved in core packing or found at the interface between fragments. Surprisingly, however, mutation of a nonconserved surface‐exposed aspartic acid to alanine was found to have a significant effect on complementation. A single additional mutation of arginine to aspartic acid allowed for recovery of native structure and increased the thermal stability of the designed Src‐p85 chimera by 18°C. This modification appears to relieve an unfavorable surface electrostatic interaction, demonstrating the importance of surface charge interactions in protein stability.
Stably folded de novo proteins from a designed combinatorial library
Authors: Wei Yinan , Liu Tun , Sazinsky Stephen L. , Moffet David A. , Pelczer István , Hecht Michael H.
Published: August 2003

Binary patterning of polar and nonpolar amino acids has been used as the key design feature for constructing large combinatorial libraries of de novo proteins. Each position in a binary patterned sequence is designed explicitly to be either polar or nonpolar; however, the precise identities of these amino acids are varied extensively. The combinatorial underpinnings of the “binary code” strategy preclude explicit design of particular side chains at specified positions. Therefore, packing interactions cannot be specified a priori. To assess whether the binary code strategy can nonetheless produce well‐folded de novo proteins, we constructed a second‐generation library based upon a new structural scaffold designed to fold into 102‐residue four‐helix bundles. Characterization of five proteins chosen arbitrarily from this new library revealed that (1) all are α‐helical and quite stable; (2) four of the five contain an abundance of tertiary interactions indicative of well‐ordered structures; and (3) one protein forms a well‐folded structure with native‐like features. The proteins from this new 102‐residue library are substantially more stable and dramatically more native‐like than those from an earlier binary patterned library of 74‐residue sequences. These findings demonstrate that chain length is a crucial determinant of structural order in libraries of de novo four‐helix bundles. Moreover, these results show that the binary code strategy—if applied to an appropriately designed structural scaffold—can generate large collections of stably folded and/or native‐like proteins.
A structural basis for the mechanism of aspartate‐β‐semialdehyde dehydrogenase from Vibrio cholerae
Authors: Blanco Julio , Moore Roger A. , Kabaleeswaran Venkataraman , Viola Ronald E.
Published: August 2003

L‐Aspartate‐β‐semialdehyde dehydrogenase (ASADH) catalyzes the reductive dephosphorylation of β‐aspartyl phosphate to L‐aspartate‐β‐semialdehyde in the aspartate biosynthetic pathway of plants and micro‐organisms. The aspartate pathway produces fully one‐quarter of the naturally occurring amino acids, but is not found in humans or other eukaryotic organisms, making ASADH an attractive target for the development of new antibacterial, fungicidal, or herbicidal compounds. We have determined the structure of ASADH from Vibrio cholerae in two states; the apoenzyme and a complex with NADP, and a covalently bound active site inhibitor, S‐methyl‐L‐cysteine sulfoxide. Upon binding the inhibitor undergoes an enzyme‐catalyzed reductive demethylation leading to a covalently bound cysteine that is observed in the complex structure. The enzyme is a functional homodimer, with extensive intersubunit contacts and a symmetrical 4‐amino acid bridge linking the active site residues in adjacent subunits that could serve as a communication channel. The active site is essentially preformed, with minimal differences in active site conformation in the apoenzyme relative to the ternary inhibitor complex. The conformational changes that do occur result primarily from NADP binding, and are localized to the repositioning of two surface loops located on the rim at opposite sides of the NADP cleft.
Weak alignment offers new NMR opportunities to study protein structure and dynamics
Authors: Bax Ad
Published: August 2003

Protein solution nuclear magnetic resonance (NMR) can be conducted in a slightly anisotropic environment, where the orientational distribution of the proteins is no longer random. In such an environment, the large one‐bond internuclear dipolar interactions no longer average to zero and report on the average orientation of the corresponding vectors relative to the magnetic field. The desired very weak ordering, on the order of 10−3, can be induced conveniently by the use of aqueous nematic liquid crystalline suspensions or by anisotropically compressed hydrogels. The resulting residual dipolar interactions are scaled down by three orders of magnitude relative to their static values, but nevertheless can be measured at high accuracy. They are very precise reporters on the average orientation of bonds relative to the molecular alignment frame, and they can be used in a variety of ways to enrich our understanding of protein structure and function. Applications to date have focused primarily on validation of structures, determined by NMR, X‐ray crystallography, or homology modeling, and on refinement of structures determined by conventional NMR approaches. Although de novo structure determination on the basis of dipolar couplings suffers from a severe multiple minimum problem, related to the degeneracy of dipolar coupling relative to inversion of the internuclear vector, a number of approaches can address this problem and potentially can accelerate the NMR structure determination process considerably. In favorable cases, where large numbers of dipolar couplings can be measured, inconsistency between measured values can report on internal motions.
The solution structure of bovine pancreatic trypsin inhibitor at high pressure
Authors: Williamson Michael P. , Akasaka Kazuyuki , Refaee Mohamed
Published: August 2003

The solution structure of bovine pancreatic trypsin inhibitor (BPTI) at a pressure of 2 kbar is presented. The structure was calculated as a change from an energy‐minimized low‐pressure structure, using 1H chemical shifts as restraints. The structure has changed by 0.24 Å RMS, and has almost unchanged volume. The largest changes as a result of pressure are in the loop 10–16, which contains the active site of BPTI, and residues 38–42, which are adjacent to buried water molecules. Hydrogen bonds are compressed by 0.029 ± 0.117 Å, with the longer hydrogen bonds, including those to internal buried water molecules, being compressed more. The hydrophobic core is also compressed, largely from reduction of packing defects. The parts of the structure that have the greatest change are close to buried water molecules, thus highlighting the importance of water molecules as the nucleation sites for volume fluctuation of proteins in native conditions.
Efficient biosynthetic incorporation of tryptophan and indole analogs in an integral membrane protein
Authors: Broos Jaap , Gabellieri Edi , Biemans‐Oldehinkel Esther , Strambini Giovanni B.
Published: August 2003

Biosynthetic incorporation of tryptophan (Trp) analogs such as 7‐azatryptophan, 5‐hydroxytryptophan, and fluorotryptophan into a protein can facilitate its structural analysis by spectroscopic techniques such as fluorescence, phosphorescence, nuclear magnetic resonance, and Fourier transform infrared. Until now, the approach has dealt primarily with soluble proteins. In this article, we demonstrate that four different Trp analogs can be very efficiently incorporated into a membrane protein as demonstrated for the mannitol transporter of Escherichia coli (EIImtl). EIImtl overexpression was under control of the λPR promoter, and the E. coli Trp auxotroph M5219 was used as host. This strain constitutively expresses the heat labile repressor protein of the λPR promoter. Together with the presence of the repressor gene on the EIImtl plasmid, this resulted in a tightly controlled promoter system, a prerequisite for high Trp analog incorporation. A new method for determining the analog incorporation efficiency is presented that is suitable for membrane proteins. The procedure involves fitting of the phosphorescence spectrum as a linear combination of the Trp and Trp analog contributions, taking into account the influence of the protein environment on the Trp analog spectrum. The data show that the analog content of EIImtl samples is very high (>95%). In addition, we report here that biosynthetic incorporation of Trp analogs can also be effected with less expensive indole analogs, which in vivo are converted to L‐Trp analogs.
The binding of β‐ and γ‐cyclodextrins to glycogen phosphorylase b: Kinetic and crystallographic studies
Authors: Pinotsis Nikos , Leonidas Demetres D. , Chrysina Evangelia D. , Oikonomakos Nikos G. , Mavridis Irene M.
Published: August 2003

A number of regulatory binding sites of glycogen phosphorylase (GP), such as the catalytic, the inhibitor, and the new allosteric sites are currently under investigation as targets for inhibition of hepatic glycogenolysis under high glucose concentrations; in some cases specific inhibitors are under evaluation in human clinical trials for therapeutic intervention in type 2 diabetes. In an attempt to investigate whether the storage site can be exploited as target for modulating hepatic glucose production, α‐, β‐, and γ‐cyclodextrins were identified as moderate mixed‐type competitive inhibitors of GPb (with respect to glycogen) with Ki values of 47.1, 14.1, and 7.4 mM, respectively. To elucidate the structural basis of inhibition, we determined the structure of GPb complexed with β‐ and γ‐cyclodextrins at 1.94 Å and 2.3 Å resolution, respectively. The structures of the two complexes reveal that the inhibitors can be accommodated in the glycogen storage site of T‐state GPb with very little change of the tertiary structure and provide a basis for understanding their potency and subsite specificity. Structural comparisons of the two complexes with GPb in complex with either maltopentaose (G5) or maltoheptaose (G7) show that β‐ andγ‐cyclodextrins bind in a mode analogous to the G5 and G7 binding with only some differences imposed by their cyclic conformations. It appears that the binding energy for stabilization of enzyme complexes derives from hydrogen bonding and van der Waals contacts to protein residues. The binding of α‐cyclodextrin and octakis (2,3,6‐tri‐O‐methyl)‐γ‐cyclodextrin was also investigated, but none of them was bound in the crystal; moreover, the latter did not inhibit the phosphorylase reaction.
Backbone and side–chain heteronuclear resonance assignments and hyperfine NMR shifts in horse cytochrome c
Authors: Liu Weixia , Rumbley Jon , Englander S. Walter , Wand A. Joshua
Published: August 2003

The [H26N, H33N] mutant of horse heart cytochrome c was expressed in E. coli during growth on isotopically enriched minimal media. Complete resonance assignments of both the diamagnetic reduced (spin zero) and paramagnetic oxidized (spin ½) states of the protein were obtained using standard triple resonance and total correlation spectroscopy using the previously determined 1H chemical shifts of the wild‐type protein as a guide. The correspondence of chemical shifts between the wild type and the mutant protein is excellent, indicating that they have nearly identical structures. The expanded library of chemical shifts for both redox states in both proteins allowed the refinement of the electron spin g‐tensor of the oxidized states. The g‐tensors of the oxidized states of the wild‐type and [H26N, H33N] mutant proteins are closely similar, indicating that the subtle details of the ligand fields are nearly identical. The refined g‐tensors were then used to probe for redox‐dependent structure change in the two proteins.
Opposing effects of phosphoenolpyruvate and pyruvate with Mg2+ on the conformational stability and dimerization of phosphotransferase enzyme I from Escherichia coli
Authors: Dimitrova Mariana N. , Peterkofsky Alan , Ginsburg Ann
Published: August 2003

The activity of enzyme I (EI), the first protein in the bacterial PEP:sugar phosphotransferase system, is regulated by a monomer‐dimer equilibrium where a Mg2+‐dependent autophosphorylation by PEP requires the homodimer. Using inactive EI(H189A), in which alanine is substituted for the active‐site His189, substrate‐binding effects can be separated from those of phosphorylation. Whereas 1 mM PEP (with 2 mM Mg2+) strongly promotes dimerization of EI(H189A) at pH 7.5 and 20°C, 5 mM pyruvate (with 2 mM Mg2+) has the opposite effect. A correlation between the coupling of N‐ and C‐terminal domain unfolding, measured by differential scanning calorimetry, and the dimerization constant for EI, determined by sedimentation equilibrium, is observed. That is, when the coupling between N‐ and C‐terminal domain unfolding produced by 0.2 or 1.0 mM PEP and 2 mM Mg2+ is inhibited by 5 mM pyruvate, the dimerization constant for EI(H189A) decreases from > 108 to < 5 × 105 or 3 × 107 M−1, respectively. Incubation of the wild‐type, dephospho‐enzyme I with the transition‐state analog phosphonopyruvate and 2 mM Mg2+ also increases domain coupling and the dimerization constant ∼42‐fold. With 2 mM Mg2+ at 15–25°C and pH 7.5, PEP has been found to bind to one site/monomer of EI(H189A) with KA′ ≈ 106 M−1 (ΔG′ = −8.05 ± 0.05 kcal/mole and ΔH = +3.9 kcal/mole at 20°C); ΔCp = −0.33 kcal K−1 mole−1. The binding of PEP to EI(H189A) is synergistic with that of Mg2+. Thus, physiological concentrations of PEP and Mg2+ increase, whereas pyruvate and Mg2+ decrease the amount of dimeric, active, dephospho‐enzyme I.
Rationally selected basis proteins: A new approach to selecting proteins for spectroscopic secondary structure analysis
Authors: Oberg Keith A. , Ruysschaert Jean‐Marie , Goormaghtigh Erik
Published: August 2003

Protein basis sets have been extensively used as reference data for the determination of protein structure with optical methods such as circular dichroism and infrared spectroscopies. We have taken a new approach to basis protein selection by utilizing three crystal structure classification databases: CATH, SCOP, and PDB_SELECT. Through the use of the information available in these and other online resources, we identified 115 commercially available proteins as potential basis set candidates. By carefully screening the quality of the crystal structures and commercial protein preparations, we obtained a final set of 50 rationally selected proteins (RaSP50) that has been optimized for use in spectroscopic protein structure determination studies. These proteins span the full range of known protein folds as well as α‐helix and β‐sheet contents, and they represent a more comprehensive variety of fold types than any previous reference set. This report includes a detailed presentation of the reasoning behind the rational protein selection process, a description of the properties of the RaSP50 set, and a discussion of the types of structural and spectral variations that are represented in the set.
Homology modeling provides insights into the binding mode of the PAAD/DAPIN/pyrin domain, a fourth member of the CARD/DD/DED domain family
Authors: Liu Tong , Rojas Ana , Ye Yuzhen , Godzik Adam
Published: August 2003

The PAAD/DAPIN/pyrin domain is the fourth member of the death domain superfamily, but unlike other members of this family, it is involved not only in apoptosis but also in innate immunity and several other processes. We have identified 40 PAAD domain‐containing proteins by extensively searching the genomes of higher eukaryotes and viruses. Phylogenetic analyses suggest that there are five categories of PAAD domains that correlate with the domain architecture of the entire proteins. Homology models built on CARD and DD structures identified functionally important residues by studying conservation patterns on the surface of the models. Surface maps of each subfamily show different distributions of these residues, suggesting that domains from different subfamilies do not interact with each other, forming independent regulatory networks. Helix3 of PAAD is predicted to be critical for dimerization. Multiple alignment analysis and modeling suggest that it may be partly disordered, following a new paradigm for interaction proteins that are stabilized by protein–protein interactions.
Discrete restraint‐based protein modeling and the Cα‐trace problem
Authors: DePristo Mark A. , de Bakker Paul I.W. , Shetty Reshma P. , Blundell Tom L.
Published: August 2003

We present a novel de novo method to generate protein models from sparse, discretized restraints on the conformation of the main chain and side chain atoms. We focus on Cα‐trace generation, the problem of constructing an accurate and complete model from approximate knowledge of the positions of the Cα atoms and, in some cases, the side chain centroids. Spatial restraints on the Cα atoms and side chain centroids are supplemented by constraints on main chain geometry, φ/ξ angles, rotameric side chain conformations, and inter‐atomic separations derived from analyses of known protein structures. A novel conformational search algorithm, combining features of tree‐search and genetic algorithms, generates models consistent with these restraints by propensity‐weighted dihedral angle sampling. Models with ideal geometry, good φ/ξ angles, and no inter‐atomic overlaps are produced with 0.8 Å main chain and, with side chain centroid restraints, 1.0 Å all‐atom root‐mean‐square deviation (RMSD) from the crystal structure over a diverse set of target proteins. The mean model derived from 50 independently generated models is closer to the crystal structure than any individual model, with 0.5 Å main chain RMSD under only Cα restraints and 0.7 Å all‐atom RMSD under both Cα and centroid restraints. The method is insensitive to randomly distributed errors of up to 4 Å in the Cα restraints. The conformational search algorithm is efficient, with computational cost increasing linearly with protein size. Issues relating to decoy set generation, experimental structure determination, efficiency of conformational sampling, and homology modeling are discussed.
Refolding out of guanidine hydrochloride is an effective approach for high‐throughput structural studies of small proteins
Authors: Maxwell Karen L. , Bona Diane , Liu Chengsong , Arrowsmith Cheryl H. , Edwards Aled M.
Published: August 2003

Low in vivo solubility of recombinant proteins expressed in Escherichia coli can seriously hinder the purification of structural samples for large‐scale proteomic NMR and X‐ray crystallography studies. Previous results from our laboratory have shown that up to one half of all bacterial and archaeal proteins are insoluble when overexpressed in E. coli. Although a number of strategies may be used to increase in vivo protein solubility, there are no generally applicable methods, and the expression of each insoluble recombinant protein must be individually optimized. For this reason, we have tested a generic denaturation/refolding protein purification procedure to assess the number of structural samples that could be generated by using this methodology. Our results show that a denaturation/refolding protocol is appropriate for many small proteins (≤18 kD) that are normally soluble in vivo. In addition, refolding the purified proteins by using dialysis against a single buffer allowed us to obtain soluble protein samples of 58% of small proteins that were found in the insoluble fraction in vivo, and 10% of the initial number of proteins provided good heteronuclear single quantum coherence (HSQC) NMR spectra. We conclude that a denaturation/refolding protocol is an efficient way to generate structural samples for high‐throughput studies of small proteins.
Lipid–binding proteins: Structure of the phospholipid ligands
Authors: Marsh Derek
Published: August 2003

Dihedral angles are evaluated for the phospholipid ligands of the lipid‐binding proteins found in the Protein Data Base (PDB). Phospholipid structures occur with a trans C1–C2 configuration of the glycerol backbone and oppositely extended chains, in addition to the gauche C1–C2 rotamers found in membranes. Headgroup conformations are not restricted to the single bent‐down configuration and gauche–gauche configuration of the phosphodiester that is found in phospholipid crystals. Additionally, fully extended headgroups and orientations directed away from the lipid chains are found for phospholipids in the protein binding pockets. On average, the hydrocarbon chains of the protein‐bound lipids are conformationally more disordered than in fluid bilayer membranes. However, much of this configurational disorder arises from energetically disallowed skew conformations. This suggests a configurational heterogeneity in the lipids at a single binding site: Eclipsed conformations occur also in some lipid headgroups and glycerol backbones. Stereochemical violations appear for some of the ester carboxyl groups of the protein‐bound phospholipids in the PDB, and two glycerol backbones have the incorrect enantiomeric configuration.
Evidence from panel unit root and cointegration tests that the Environmental Kuznets Curve does not exist
Authors: Perman Roger , Stern David I.
Published: August 2003

The Environmental Kuznets Curve (EKC) hypothesis – an inverted U‐shape relation between various indicators of environmental degradation and income per capita – has become one of the ‘stylised facts’ of environmental and resource economics. This is despite considerable criticism on both theoretical and empirical grounds. Cointegration analysis can be used to test the validity of such stylised facts when the data involved contain stochastic trends. In the present paper, we use cointegration analysis to test the EKC hypothesis using a panel dataset of sulfur emissions and GDP data for 74 countries over a span of 31 years. We find that the data is stochastically trending in the time‐series dimension. Given this, and interpreting the EKC as a long run equilibrium relationship, support for the hypothesis requires that an appropriate model cointegrates and that sulfur emissions are a concave function of income. Individual and panel cointegration tests cast doubt on the general applicability of the hypothesised relationship. Even when we find cointegration, many of the relationships for individual countries are not concave. The results show that the EKC is a problematic concept, at least in the case of sulfur emissions.
Agricultural and resource economics and economic development in Aboriginal communities
Authors: Duncan Ron
Published: August 2003

Economic development is seen as the best way for Aboriginal communities to improve their welfare and lessen the considerable disadvantages they suffer. Unfortunately, the economics profession has shown little interest in their plight. Agricultural and resource economists have much to offer in helping to foster economic development in Aboriginal communities throughout Australia. Suggestions are made as to various ways in which our particular interests and experiences can hopefully be applied.
Agricultural trade in North America: Trade creation, regionalism and regionalisation
Authors: Miljkovic Dragan , Paul Rodney
Published: August 2003

Trade creation in agricultural products is defined as a statistically significant positive break in the trend function of the growth in exports and imports between member countries. The present study attempts to determine the time of any break in the trend of real exports and imports between the Canada–USA Free Trade Agreement (CUSTA) and the North American Free Trade Agreement (NAFTA) member countries for the years 1980:I through 1999:II, and document the scale of the phenomenon. The present study finds trade creation only occurs in USA agricultural exports to Canada because of CUSTA. The results confirm the theory that the regionalism of NAFTA did not lead to regionalisation or an increasing share of intraregional international trade.
An evolutionary economic perspective on technical change and adjustment in cane harvesting systems in the Australian sugar industry
Authors: Brennan Lisa , Malcolm Wegener
Published: August 2003

Australian sugar‐producing regions have differed in terms of the extent and rate of incorporation of new technology into harvesting systems. The Mackay sugar industry has lagged behind most other sugar‐producing regions in this regard. The reasons for this are addressed by invoking an evolutionary economics perspective. The development of harvesting systems, and the role of technology in shaping them, is mapped and interpreted using the concept of path dependency. Key events in the evolution of harvesting systems are identified, which show how the past has shaped the regional development of harvesting systems. From an evolutionary economics perspective, the outcomes observed are the end result of a specific history.
Economic policy for rural and regional Australia
Authors: Freebairn John
Published: August 2003

The efficiency and equity effects of economic policies affecting the quarter of Australians who live in rural and regional Australia (RARA) are reviewed. For the most part it is argued that economy‐wide policies, rather than region or industry specific policies, are appropriate. Progressive income taxation, means‐tested social security payments and government funded education, health and other services directly and efficiently redistribute to support equity. Subsidies for particular industries in RARA, such as dairy, and input subsidies targeted at RARA, such as community service obligations, misallocate resources and are ineffective in meeting equity goals. Better property rights and procedures for allocating most natural resources, especially water, are necessary.
Hazardous Facility Siting When Cost Information Is Private: An Application of Multidimensional Mechanism Design
Authors: Waehrer Keith
Published: August 2003

The siting of hazardous facilities often involves externalities that extend beyond the border of the community selected as a site. Thus, the private information of each community is potentially a vector of costs comprising a cost for each of the possible sites. I characterize the conditions for the existence of a direct mechanism that is incentive compatible, individually rational, and budget balancing. Incentive compatibility implies a pattern of compensation payments that often conflicts with compensation policy goals. When nonparticipating communities cannot block the siting of the facility, it will often be possible to implement siting policies with a balanced budget.
On the Use of Incentive Pay in Chinese State‐owned Enterprises: The Role of Hierarchy
Authors: Bodmer Frank
Published: August 2003

Abstract.  This paper looks at the wage system in Chinese state‐owned enterprises (SOEs) during the 1980s. While wages remained compressed, there is evidence for the use of incentive mechanisms. Wages were quite sensitive to firm performance, especially at higher levels of the hierarchy. One of the reform measures — the Internal Salary System, a system of intra‐firm contracts — has contributed significantly to this sensitivity. There is also some direct evidence that it enhanced the effectiveness of the bonus system, and that it helped to increase productivity. This goes towards explaining how the Chinese bonus system was able to overcome the free‐rider problems typical of team compensation.
Can Pay‐as‐You‐Go Pensions Raise the Capital Stock?
Authors: Roberts Mark A.
Published: August 2003

We reconsider pay‐as‐you‐go (PAYG) pension policy in a version of the Diamond overlapping generations model with an imperfectly competitive financial sector and with a low rate of tax on its profits. PAYG then has two effects on capital: the well‐known negative crowding‐out effect in displacing savings and a positive effect in reducing a second form of crowding‐out caused by the displacement of ‘productive savings’ in capital by ‘non‐productive savings’ in financial sector equity. These two countervailing effects may generate a hump‐shaped steady‐state relationship between the PAYG contribution rate and the capital stock.
Behavioural Central Bank Loss Functions, Skewed Risks and Certainty Equivalence
Authors: Al‐Nowaihi Ali , Stracca Livio
Published: August 2003

We set out to investigate the role of additive uncertainty under behaviourally plausible non‐standard central bank loss functions on future inflation. Building on a substantial body of evidence in the economic psychology literature, we propose (i) period‐by‐period loss functions that are non‐convex, i.e. displaying diminishing or non‐increasing sensitivity to losses, and (ii) non‐linear weighting of probabilities, hence departing from the expected utility paradigm. The main conclusion of the study is that if the additive uncertainty is caused by a non‐normal distributed additive shock, for instance if the probability distribution of the shock is skewed, then with these departures from the quadratic function the principle of certainty equivalence does not hold anymore.
Purchasing Power Parity Adjustment Speeds in High Frequency Data when the Equilibrium Real Exchange Rate is Proxied by a Deterministic Trend
Authors: Paya Ivan , Peel David A.
Published: August 2003

Rogoff suggested in 1996 that the dollar–yen real exchange rate represented a ‘canonical’ case of a trend in the equilibrium real exchange rate. The implied speed of adjustment of the dollar–yen real exchange rate is found to be substantially faster, with half‐life shocks of less than 2 years, from estimates of a non‐linear model which incorporates a deterministic trend proxying the equilibrium level. We also examine the power of unit root tests against smooth transition non‐linear models which incorporate a deterministic trend and the robustness of such non‐linear estimations using Monte Carlo and bootstrap simulations.
Testing the Expectations Hypothesis of the Term Structure of Interest Rates in the Presence of a Potential Regime Shift
Authors: Lanne Markku
Published: August 2003

The expectations hypothesis of the term structure of interest rates is tested with monthly Eurodollar deposit rates for maturities of 1, 3 and 6 months covering the period 1983:1–1999:6. Classical regression based tests indicate rejection, while tests in a new model allowing for potential regime shifts that have not occurred in the sample period lend support to the expectations hypothesis. The results imply that the potential regime shift affected the expectations concerning the longer‐term interest rate only in a short period at the beginning of the sample when the interest rates were highest.
Testing for Common Cycles in Money, Nominal Income and Prices
Authors: Hall Stephen , Shepherd David
Published: August 2003

In this paper we consider whether common cyclical dynamics can be identified in the money–inflation relationships suggested by the quantity theory of money. The analysis is based on an examination of data for the USA and the UK, using correlation methods and the more stringent common features test developed by Engle and Kozicki. We discuss the nature of the test procedures and the results from the common features test are compared with those obtained from the more traditional correlation analysis. The results of the analysis are mixed, but are generally supportive of the quantity theory.
ANTI‐GLOBALISATION: BAD WINE IN NEW BOTTLES?
Authors: Ryder Andrew
Published: August 2003

Many opponents of globalisation claim that global finance and trade are manipulated in the name of liberalism by a few people and firms, supported by the international media. They argue that democracy should be abandoned and economic and social change resisted. They have widespread support in the intellectual community. Similar views were espoused by the far right wing in the 1920s and 1930s, and disappeared only with the collapse of Nazism and Fascism. Their reappearance parallels the return to legitimacy of the political far right.
COMPETITION AMONG STAKEHOLDER GROUPS FOR POLITICAL INFLUENCE OVER BUSINESS REGULATION: THE CASE OF THE UK PENSIONS INDUSTRY
Authors: Klumpes Paul
Published: August 2003

This paper applies a stakeholder perspective to estimate various types of costs (taxes) and benefits (subsidies) affecting stakeholder groups whose constituents are most affected by recent, major reforms to the public regulation of the UK pensions industry. Both direct and indirect subsidies and taxes arising from regulation distinguishes groups representing both sophisticated and vulnerable investors. The analysis suggests that financial intermediaries, and industry regulators, are all effectively subsidised by other stakeholder groups.
HOW TO CLEAR UP THE PENSIONS MESS
Authors: Simpson David
Published: August 2003

All three pillars of the British pensions system are crumbling. The basic state pension is unsustainable in its present form. Defined benefit occupational pension schemes are fast disappearing, and with them the retirement hopes of millions of workers. A further 3 million low‐income earners are not saving enough for their retirement. And uncertainty about pensions choices is widespread. In each case the primary cause of the problem is governmental or regulatory failure. The paper makes eight general and four specific proposals for restoring the system.
THE REGULATION OF LIFE ASSURERS IN A LOW SOLVENCY ENVIRONMENT: THE UK EXPERIENCE
Authors: O'Brien Chris
Published: August 2003

When adverse financial conditions mean that many life assurers have sharply reduced solvency levels, a number of new issues arise for regulators, including the basic issue of how solvency is measured. There are also issues about life assurers' investments, and their products and how they are priced. Lastly, the regulator (in the UK, the Financial Services Authority) needs to ensure that customers and their advisers have suitable information about the solvency of the firms they are dealing with.
TOO MUCH REGULATION?
Authors: Wood Geoffrey E.
Published: August 2003

This paper considers the purposes that regulation and supervision of financial institutions are designed to serve. Historical experience with regulation and supervision is considered, and it is argued on the basis of that examination that a fairly ‘light touch’ in regulation is likely to achieve the objectives that governments and citizens require regulation to achieve. Accordingly, the paper concludes that when regulation is evaluated and compared with unregulated systems, one should be careful to compare fallible regulation with fallible markets, rather than implicitly assuming regulation is perfect. Otherwise over‐regulation will result.
WHO SHOULD REGULATE FINANCIAL INSTITUTIONS?
Authors: Booth Philip
Published: August 2003

Financial market transactions involve complex decisions and significant amounts of information have to be processed by consumers. Economists often call for statutory regulation to overcome so‐called ‘information asymmetries.’ However, the market will generally develop sophisticated institutions that are able to deal with such problems in financial markets. It is important that regulators do not impede the development of such institutions. The liberal market structure may not look like the market structures in many textbook models of so‐called ‘perfect’ markets. However, the structure may well be efficient and welfare enhancing.
MORE NONSENSE ON STILTS: MR BENTHAM IS AT IT AGAIN
Authors: de Jasay Anthony
Published: August 2003

Lord Layard recently suggested in a series of lectures at the LSE that economists should be concerned with developing policies to maximise human happiness. His bold resurrection of the Benthamite school invites the most forceful criticism that can be levelled against naïve utilitarianism.
THE ORIGINS OF LIBERTY AND THE MARKET: THE WORK OF MARJORIE GRICEHUTCHINSON (1909–2003)
Authors: Barry Norman
Published: August 2003

Marjorie Grice‐Hutchinson, who recently died, was a leading scholar of the Salamanca school of economics. That school anticipated much of the economic thinking which helped underpin the case for liberal markets in the eighteenth and nineteenth centuries.
SIMPLIFYING THE TAXATION OF PENSIONS
Authors: Booth Philip , Cooper Deborah
Published: August 2003

The current tax framework for pensions is now economically incoherent. The changes in the 1997 Budget made it more so. Changes can be made to restore its coherence. However, any attempt to remove tax relief at the higher rate, as has been discussed by academics and commentators recently, would be wrong in principle and could not work in practice. The pension fund tax codes and the rules for annuitisation should also be simplified significantly. The Inland Revenue no longer needs to design detailed rules to prevent people ‘abusing’ tax relief. Such detailed rules are extremely costly to implement and, because they make the whole system impenetrable, stop people from using pension vehicles for saving.
Representational Projects and Interacting Forms of Knowledge
Authors: Foster Juliet L.H.
Published: August 2003

This paper focuses on the concept of the reified and consensual universes in the theory of social representations, and the relationship between them. Having examined the different ways in which Moscovici discusses this concept, and the different ways in which these discussions have been interpreted, I will suggest that many of the criticisms levelled at this facet of social representations theory appear somewhat misplaced. However, it does seem that some aspects of the concept of the consensual and the reified universes are rather under‐developed within the theory as a whole. It will be suggested that the recent addition of the notion of the representational project to the theory of social representations goes some way towards addressing some of these emergent issues, most notably with regards to the relationship between knowledges from different spheres. As an example, the area of representations of health and illness will be considered: drawing on work that takes the perspective of the sociology of scientific knowledge, it will be suggested that the theory of social representations needs to make the possibility of a bi‐directional relationship between knowledge from the fields of scientific and common sense understanding more explicit.
The Secret Life of Things: Rethinking Social Ontology
Authors: Marcoulatos Iordanis
Published: August 2003

Despite a recent resurgence of interest in social ontology, the standard conceptualization of social/cultural objects reiterates dichotomies such as nature and culture, subjectivity and objectivity: the objective components of a social/cultural environment are usually divided into their (symbolically vacuous) material substratum, natural or manufactured, and their imposed or assigned social import. Inert materiality and subjectively or intersubjectively assigned meanings and functions remain distinct as constitutive aspects of a reality that is intuitively experienced as a whole. In contrast—by means of examining a broad range of natural/cultural entities—I propose an experiential or visceral ontology of the social, which addresses the comprehensive nature of our experience of cultural objects, as well as their perpetual transmutability within the space between nature and culture, objectivity and subjectivity. This perspective allows for a cathexis of meaning in the material constitution of cultural entities—in contrast to a mere imposition of detachable layers of meaning—and suggests a reconsideration of our unexamined perception of social/political action as editorial supervision and correction. Moreover, I point out the centrality of the concept of practice for recovering the lived sense of social things, since practice, by virtue of its inalienable informality, constitutes the field of Protean renewal of this sense. I understand my approach as complementary to the body‐turn in contemporary social theory, since I extend the postulation of meaningfulness in the objective aspect of subjective existence (i.e. the body) towards its lived surroundings, which are here perceived as engaged in a process of meaningful practiced reciprocations with corporeal subjectivities.