Biochemistry, Biophysics, and Structural Biology Commons^™

Distributions Of Trace Gases And Aerosols During The Dry Biomass Burning Season In Southern Africa, Parikhit Sinha, Peter V. Hobbs, Robert J. Yokelson, Donald R. Blake, Song Gao, Thomas W. Kirschsetter

Chemistry and Biochemistry Faculty Publications

[1] Vertical profiles in the lower troposphere of temperature, relative humidity, sulfur dioxide (SO₂), ozone (O₃), condensation nuclei (CN), and carbon monoxide (CO), and horizontal distributions of twenty gaseous and particulate species, are presented for five regions of southern Africa during the dry biomass burning season of 2000. The regions are the semiarid savannas of northeast South Africa and northern Botswana, the savanna-forest mosaic of coastal Mozambique, the humid savanna of southern Zambia, and the desert of western Namibia. The highest average concentrations of carbon dioxide (CO₂), CO, methane (CH₄), O_{3 …}

Trace Gas Measurements In Nascent, Aged, And Cloud-Processed Smoke From African Savanna Fires By Airborne Fourier Transform Infrared Spectroscopy (Aftir), Robert J. Yokelson, Issac T. Bertschi, Ted J. Christian, Peter V. Hobbs, Darold E. Ward, Wei Min Hao

Chemistry and Biochemistry Faculty Publications

[1] We measured stable and reactive trace gases with an airborne Fourier transform infrared spectrometer (AFTIR) on the University of Washington Convair-580 research aircraft in August/September 2000 during the SAFARI 2000 dry season campaign in Southern Africa. The measurements included vertical profiles of CO₂, CO, H₂O, and CH₄ up to 5.5 km on six occasions above instrumented ground sites and below the TERRA satellite and ER-2 high-flying research aircraft. We also measured the trace gas emissions from 10 African savanna fires. Five of these fires featured extensive ground-based fuel characterization, and two were in the …

Perilipin A Is Essential For The Translocation Of Hormone-Sensitive Lipase During Lipolytic Activation. J Cell Biol, John Tansey

Chemistry Faculty Scholarship

A key step in lipolytic activation of adipocytes is the translocation of hormone-sensitive lipase (HSL) from the cytosol to the surface of the lipid storage droplet. Adipocytes from perilipin -null animals have an elevated basal rate of lipolysis compared with adipocytes from wild-type mice, but fail to respond maximally to lipolytic stimuli. This defect is downstream of the -adrenergic receptor–adenylyl cyclase complex. Now, we show that HSL is basally associated with lipid droplet surfaces at a low level in perilipin nulls, but that stimulated translocation from the cytosol to lipid droplets is absent in adipocytes derived from embryonic fibroblasts of …

Thickness Dependence Of Magnetic Blocking In Granular Thin Films With Interacting Magnetic Particles, Jian Qing Wang, Zhi Dong Zhao, Scott L. Whittenburg

Chemistry and Biochemistry Faculty Publications

Interparticle interaction among single domain nanosize magnetic particles embedded in nonmagnetic matrix was studied. Attention was paid to concentrated Cu–Co granular thin films with a fixed magnetic volume fraction (20%). By analyzing theoretical models and comparing with experimental results, a dimensional constraint on the magnetic properties was found. As the film thickness reduces toward the thin limit the interparticle interaction plays important roles in modifying the magnetic behavior. The dipolar interaction energy was calculated among magnetic particles including far-neighbor interaction for films with different thickness values. When magnetization variation is included in the calculation, the resulting calculated interaction energy versus …

Evaluating The Effects Of Enhanced Processivity And Metal Ions On Translesion Dna Replication Catalyzed By The Bacteriophage T4 Dna Polymerase, Edmunds Z. Reineks, Anthony J. Berdis

Chemistry Faculty Publications

The fidelity of DNA replication is achieved in a multiplicative process encompassing nucleobase selection and insertion, removal of misinserted nucleotides by exonuclease activity, and enzyme dissociation from primer/templates that are misaligned due to mispairing. In this study, we have evaluated the effect of altering these kinetic processes on the dynamics of translesion DNA replication using the bacteriophage T4 replication apparatus as a model system. The effect of enhancing the processivity of the T4 DNA polymerase, gp43, on translesion DNA replication was evaluated using a defined in vitro assay system. While the T4 replicase (gp43 in complex with gp45) can perform …

Preparation Of 2s,3s-N-Isobutyl-N-(2-Hydroxy-3-Amino-4-Phenylbutyl)-P-Nitrobenzenesulfonylamide Hydrochloride And Other Derivatives Of 2-Hydroxy-1,3-Diamines, Aslam A. Malik, Hasan Palandoken, Joy A. Stringer, Roland P. Carlson, John Leach, Thomas G. Archibald, Robert G. Miotke

Chemistry and Biochemistry

The present invention provides a new process for the preparation of 2S,3S-N-isobutyl-N-(2-hydroxy-3-amino-4phenylbutyl)- p-nitrobenzenesulfonylamide hydrochloride, wherein this compound is prepared directly from the chloromethylalcohol. Importantly, the process of the present invention results in higher yields of 2S,3S-N-isobutyl-N-(2hydroxy -3 -amino -4-phenylbutyl) -pnitrobenzenesulfonylamide hydrochloride without sacrificing its purity. The processes of the present inventin can be used to prepare not only the 2S,3S-derivative, but also the 2R,3S-, 2S,2R- and the 2R,3R-derivatives.

Clean, High-Yield Preparation Of S,S- And R,S- Amino Acid Isosteres, Aslam A. Malik, Todd E. Clement, Hasan Palandoken, James Robinson Iii, Joy A. Stringer

Chemistry and Biochemistry

The present invention provides compounds and methods that can be used to convert the intermediate halomethyl ketones (HMKs), e.g., chloromethyl ketones, to the corresponding S,S- and R,S-diastereomers. More particularly, the present invention provides: (1) reduction methods; (2) inversion methods; and (3) methods involving the epoxidation of alkenes. Using the various methods of the present invention, the R,S-epoxide and the intermediary compounds can be prepared reliably, in high yields and in high purity.

Tropospheric Carbon Monoxide Measurements From The Scanning High-Resolution Interferometer Sounder On 7 September 2000 In Southern Africa During Safari 2000, W. W. Mcmillan, M. L. Mccourt, H. E. Revercomb, R. O. Knuteson, Ted J. Christian, B. G. Doddridge, Peter V. Hobbs, J. V. Lukovich, P. C. Novelli, S. J. Piketh, L. Sparling, D. Stein, R. J. Swap, Robert J. Yokelson

Chemistry and Biochemistry Faculty Publications

[1] Retrieved tropospheric carbon monoxide (CO) column densities are presented for more than 9000 spectra obtained by the University of Wisconsin-Madison (UWis) Scanning High-Resolution Interferometer Sounder (SHIS) during a flight on the NASA ER-2 on 7 September 2000 as part of the Southern African Regional Science Initiative (SAFARI 2000) dry season field campaign. Enhancements in tropospheric column CO were detected in the vicinity of a controlled biomass burn in the Timbavati Game Reserve in northeastern South Africa and over the edge of the river of smoke in south central Mozambique. Relatively clean air was observed over the far southern coast …

Emissions Of Trace Gases And Particles From Savanna Fires In Southern Africa, Parikhit Sinha, Peter V. Hobbs, Robert J. Yokelson, I. T. Bertschi, Donald R. Blake, Isobel J. Simpson, Song Gao, Thomas W. Kirschsetter, Tica Novakov

Chemistry and Biochemistry Faculty Publications

[1] Airborne measurements made on initial smoke from 10 savanna fires in southern Africa provide quantitative data on emissions of 50 gaseous and particulate species, including carbon dioxide, carbon monoxide, sulfur dioxide, nitrogen oxides, methane, ammonia, dimethyl sulfide, nonmethane organic compounds, halocarbons, gaseous organic acids, aerosol ionic components, carbonaceous aerosols, and condensation nuclei (CN). Measurements of several of the gaseous species by gas chromatography and Fourier transform infrared spectroscopy are compared. Emission ratios and emission factors are given for eight species that have not been reported previously for biomass burning of savanna in southern Africa (namely, dimethyl sulfide, methyl nitrate, …

Evolution Of Gases And Particles From A Savanna Fire In South Africa, Peter V. Hobbs, Parikhit Sinha, Robert J. Yokelson, Ted J. Christian, Donald R. Blake, Song Gao, Thomas W. Kirschsetter, Tica Novakov, Peter Pilewskie

Chemistry and Biochemistry Faculty Publications

[1] Airborne measurements of particles and gases from a 1000-ha savanna fire in South Africa are presented. These measurements represent the most extensive data set reported on the aging of biomass smoke. The measurements include total concentrations of particles (CN), particle sizes, particulate organic carbon and black carbon, light-scattering coefficients, downwelling UV fluxes, and mixing ratios for 42 trace gases and 7 particulate species. The ratios of excess nitrate, ozone, and gaseous acetic acid to excess CO increased significantly as the smoke aged over ∼40–45 min, indicating that these species were formed by photochemistry in the plume. For 17 other …

Trace Gas And Particle Emissions From Fires In Large Diameter And Belowground Biomass Fuels, Isaac T. Bertschi, Robert J. Yokelson, Darold E. Ward, R. E. Babbitt, Ronald A. Susott, Jon G. Goode, Wei Min Hao

Chemistry and Biochemistry Faculty Publications

[1] We adopt a working definition of residual smoldering combustion (RSC) as biomass combustion that produces emissions that are not lofted by strong fire-induced convection. RSC emissions can be produced for up to several weeks after the passage of a flame front and they are mostly unaffected by flames. Fuels prone to RSC include downed logs, duff, and organic soils. Limited observations in the tropics and the boreal forest suggest that RSC is a globally significant source of emissions to the troposphere. This source was previously uncharacterized. We measured the first emission factors (EF) for RSC in a series of …

Examination Of The Role Of The Clamp-Loader And Atp Hydrolysis In The Formation Of The Bacteriophage T4 Polymerase Holoenzyme, Michael A. Trakselis, Anthony J. Berdis, Stephen J. Benkovic

Chemistry Faculty Publications

Transient kinetic analyses further support the role of the clamp-loader in bacteriophage T4 as a catalyst which loads the clamp onto DNA through the sequential hydrolysis of two molecules of ATP before and after addition of DNA. Additional rapid-quench and pulse-chase experiments have documented this stoichiometry. The events of ATP hydrolysis have been related to the opening/closing of the clamp protein through fluorescence resonance energy transfer (FRET). In the absence of a hydrolysable form of ATP, the distance across the subunit interface of the clamp does not increase as measured by intramolecular FRET, suggesting gp45 cannot be loaded onto DNA. …

Trace Gas Emissions From The Production And Use Of Domestic Biofuels In Zambia Measured By Open-Path Fourier Transform Infrared Spectroscopy, Isaac T. Bertschi, Robert J. Yokelson, Darold E. Ward, Ted J. Christian, Wei Min Hao

Chemistry and Biochemistry Faculty Publications

[1] Domestic biomass fuels (biofuels) were recently estimated to be the second largest source of carbon emissions from global biomass burning. Wood and charcoal provide approximately 90% and 10% of domestic energy in tropical Africa. In September 2000, we used open-path Fourier transform infrared (OP-FTIR) spectroscopy to quantify 18 of the most abundant trace gases emitted by wood and charcoal cooking fires and an earthen charcoal-making kiln in Zambia. These are the first in situ measurements of an extensive suite of trace gases emitted by tropical biofuel burning. We report emission ratios (ER) and emission factors (EF) for (in order …

Phosphoproteomic Studies Of Smooth Muscle Contraction: Investigation Of Differential Phosphorylation In Relaxed/Contracted Rat Aortic Smooth Muscle Tissue Using Maldi-Tof Ms, Tonya M. Pekar

Theses, Dissertations and Capstones

Many human disorders are associated with the malfunction of smooth muscle tissue, or are related to the capabilities of its proper function—asthma, glaucoma, renal inefficiency, hypertension, and cardiovascular disease. Dysfunctional proteins are frequently implicated as the source of such disorders. As the second highest cause of death in the United States, the epidemic of cardiovascular disease makes the study of smooth muscle of utmost concern.

The capabilities of proteomics and mass spectrometry allow the entire proteome complement of a cell or tissue type to be analyzed at once. This investigation employs such techniques in an effort to better understand the …

Tetratricopeptide Repeat Motif-Mediated Hsc70-Msti1 Interaction Molecular Characterization Of The Critical Contacts For Successful Binding And Specificity*, Odutayo O. Odunuge, Judith A. Hornby, Chrisiane Bies, Richard Zimmermann, David J. Pugh, Gregory L. Blatch

Faculty Publications

Murine stress-inducible protein 1 (mSTI1) is a cochaperone that is homologous with the human Hsp70/ Hsp90-organizing protein (Hop). Guided by Hop structural data and sequence alignment analyses, we have used site-directed mutagenesis, co-precipitation assays, circular dichroism spectroscopy, steady-state fluorescence, and surface plasmon resonance spectroscopy to both qualitatively and quantitatively characterize the contacts necessary for the N-terminal tetratricopeptide repeat domain (TPR1) of mSTI1 to bind to heat shock cognate protein 70 (Hsc70) and to discriminate between Hsc70 and Hsp90. We have shown that substitutions in the first TPR motif of Lys8 or Asn12 did not affect binding of mSTI1 to Hsc70, …

Fluorescence Determination Of Tryptophan Side-Chain Accessibility And Dynamics In Triple-Helical Collagen-Like Peptides, K. V. Simon-Lukasik, A. V. Persikov, B. Brodsky, J. A. M. Ramshaw, William Laws, J. B. A. Ross, R. D. Ludescher

Chemistry and Biochemistry Faculty Publications

We report tryptophan fluorescence measurements of emission intensity, iodide quenching, and anisotropy that describe the environment and dynamics at X and Y sites in stable collagen-like peptides of sequence (Gly-X-Y)(n). About 90% of tryptophans at both sites have similar solvent exposed fluorescence properties and a lifetime of 8.5-9 ns. Analysis of anisotropy decays using an associative model indicates that these long lifetime populations undergo rapid depolarizing motion with a 0.5 ns correlation time; however, the extent of fast motion at the Y site is considerably less than the essentially unrestricted motion at the X site. About 10% of tryptophans at …

Constrained Analysis Of Fluorescence Anisotropy Decay: Application To Experimental Protein Dynamics, E. Feinstein, G. Deikus, E. Rusinova, E. L. Rachofsky, J. B. A. Ross, William Laws

Chemistry and Biochemistry Faculty Publications

Hydrodynamic properties as well as structural dynamics of proteins can be investigated by the well-established experimental method of fluorescence anisotropy decay. Successful use of this method depends on determination of the correct kinetic model, the extent of cross-correlation between parameters in the fitting function, and differences between the timescales; of the depolarizing motions and the fluorophore's fluorescence lifetime. We have tested the utility of an independently measured steady-state anisotropy value as a constraint during data analysis to reduce parameter cross correlation and to increase the timescales over which anisotropy decay parameters can be recovered accurately for two calcium-binding proteins. Mutant …

Protocols For Disease Classification From Mass Spectrometry Data, Michael Wagner, Dayanand Naik, Alex Pothen

Mathematics & Statistics Faculty Publications

We report our results in classifying protein matrix-assisted laser desorption/ionizationtime of flight mass spectra obtained from serum samples into diseased and healthy groups. We discuss in detail five of the steps in preprocessing the mass spectral data for biomarker discovery, as well as our criterion for choosing a small set of peaks for classifying the samples. Cross-validation studies with four selected proteins yielded misclassification rates in the 10-15% range for all the classification methods. Three of these proteins or protein fragments are down-regulated and one up-regulated in lung cancer, the disease under consideration in this data set. When cross-validation studies …

Urer, The Transcriptional Activator Of The Proteus Mirabilis Urease Gene Cluster, Is Required For Urease Activity And Virulence In Experimental Urinary Tract Infections, Jonathan D. Dattelbaum, C. Virginia Lockatell, David E. Johnson, Harry L.T. Mobley

Chemistry Faculty Publications

Proteus mirabilis, a cause of complicated urinary tract infection, produces urease, an essential virulence factor for this species. UreR, a member of the AraC/XylS family of transcriptional regulators, positively activates expression of the ure gene cluster in the presence of urea. To specifically evaluate the contribution of UreR to urease activity and virulence in the urinary tract, a ureR mutation was introduced into P. mirabilis HI4320 by homologous recombination. The isogenic ureR::aphA mutant, deficient in UreR production, lacked measurable urease activity. Expression was not detected in the UreR-deficient strain by Western blotting with monoclonal antibodies raised against UreD. Urease …

A Neural Network Method For Protein Classification, Arie D. Jones

All-Inclusive List of Electronic Theses and Dissertations

The investigation detailed in this paper attempts to utilize a Leaming Vector Quantization network in order to classify a set of mitochondrial proteins based upon their amino acid sequence. The Learning Vector Quantization network uses a nearest neighbor approach to classification. Input vectors are fed into the network, which produces output vectors. Those output vectors are then matched by means of a distance bias to a corresponding classification vector. The learning and test sets consisted of thirteen similar mitochodrial proteins from seventy-two different species. This provided a pool of over nine hundred proteins to use. Half of the species were …

Calcium Binding To Calmodulin Mutants Monitored By Domain-Specific Intrinsic Phenylalanine And Tyrosine Fluorescence, W. S. Vanscyoc, B. R. Sorensen, E. Rusinova, William Laws, J. B. A. Ross, M. A. Shea

Chemistry and Biochemistry Faculty Publications

Cooperative calcium binding to the two homologous domains of calmodulin (CaM) induces conformational changes that regulate its association with and activation of numerous cellular target proteins. Calcium binding to the pair of high-affinity sites (III and IV in the C-domain) can be monitored by observing calcium-dependent changes in intrinsic tyrosine fluorescence intensity (lambda(ex)/lambda(em) of 277/320 nm). However, calcium binding to the low-affinity sites (I and II in the N-domain) is more difficult to measure with optical spectroscopy because that domain of CaM does not contain tryptophan or tyrosine. We recently demonstrated that calcium-dependent changes in intrinsic phenylalanine fluorescence (lambdaex/lambdaem of …

Guanine And 7,8-Dihydro-8-Oxo-Guanine-Specific Oxidation In Dna By Chromium(V), Kent D. Sugden, Brooke Martin

Chemistry and Biochemistry Faculty Publications

The hexavalent oxidation state of chromium [Cr(VI)] is a well-established human carcinogen, although the mechanism of cancer induction is currently unknown. Intracellular reduction of Cr(VI) forms Cr(V), which is thought to play a fundamental role in the mechanism of DNA damage by this carcinogen. Two separate pathways of DNA damage, an oxidative pathway and a metal-binding pathway, have been proposed to account for the lesions observed in cell systems. We have used a model Cr(V) complex, N,N´-ethylenebis(salicylidene-animato)oxochromium(V) [Cr(V)-Salen], to investigate the oxidative pathway of DNA damage and to elucidate the lesions generated from this oxidation process. Reaction of Cr(V)-Salen with …

A Comparison Of The Low Mode And Monte Carlo Conformational Search Methods, Carol A. Parish, Rosina Lombardi, Kent Sinclair, Emelyn Smith, Alla Goldberg, Melissa Rappleye, Myrianne Dure

Chemistry Faculty Publications

The Low Mode (LM) and Monte Carlo (MC) conformational search methods were compared on three diverse molecular systems; (4R, 5S, 6S, 7R)-hexahydro-5,6-dihydroxy-1,3,4,7-tetrakis(phenylmethyl)-2H-1,3-diazapin-2-one (1), 2-methoxy-2-phenyl-2-triflouromethyl-N-α-methyl benzyl propanamide (2) and a trimeric 39-membered polyazamacrolide (3). We find that either method, or a combination of the methods, is equally efficient at searching the conformational space of the smaller molecular systems while a 50:50 hybrid of Low Mode and Monte Carlo is most efficient at searching the space of the larger molecular system.

Monte Carlo Simulation On The Indirect Exchange Interactions Of Co-Doped Zno Film, Abraham F. Jalbout, Hanning Chen, Scott L. Whittenburg

Chemistry and Biochemistry Faculty Publications

Monte Carlo simulations using a three-dimensional lattice model studied the Ruderman–Kittel–Kasuya–Yosida (RKKY) indirect exchange interaction of doped magnetic Co ions in ZnOfilms. The results of the calculations show that the RKKY interaction in Co-doped ZnO is long ranged and its magnitude is proportional to (inverse of the distance from a central ion). The sign oscillates with a frequency that depends on the concentration of the carrier. The long-distance sum of the RKKY indirect exchange energies is positive indicating that these materials are ferromagnetic, in direct correlation with previously reported results.

Comparison Of Water Quality, Zooplankton Density, And Cover In Razorback Sucker (Xyrauchen Texanus [Abbott]) Spawning Areas Of Lake Mead And Lake Mohave, Michael E. Golden, Paul B. Holden, Southern Nevada Water Authority

Publications (WR)

Las Vegas Bay and Echo Bay in Lake Mead have small, self-sustaining populations of razorback sucker (Xyrauchen texanus [Abbot]). Increased productivity and cover have been hypothesized as reasons for successful recruitment of razorback sucker in Lake Mead. Conversely, reproduction has been documented on Lake Mohave, another lower Colorado River reservoir, but no recruitment has been observed. In 2000, BIO-WEST, Inc. was contracted by the Southern Nevada Water Authority to design and implement a study to examine nutrient levels, zooplankton density, and cover in areas with and without razorback sucker recruitment success. We sampled Echo Bay, Las Vegas Bay, and …

Magnetization Reversal Of Elliptical Co/Cu/Co Pseudo-Spin Valve Dots, Ngocnga Dao, Scott L. Whittenburg, Y. Hao, Leszek M. Malkinski, Jian Qing Wang, C. A. Ross

Chemistry and Biochemistry Faculty Publications

We present our recent simulated results on Cr (5 nm)/ Cu (5 nm)/ Co (5 nm)/ Cu (3 nm)/ Co (2 nm) pseudo-spin valve dots. The simulated results agree qualitatively with the experimental results. Three different sizes of elliptical dots, and were simulated. Our simulations show that in these types of dots magnetization reversal occurs by the formation of domain walls: for and for No domain wall was observed in the reversal of the dots. For such dots, the simulated loops show a small two-step reversal pattern with the thin upper layer partially reversing followed by complete reversal of both …

1080 Summary Information, Department Of Agriculture, Western Australia, Department Of Conservation And Land Management, Western Australia, Department Of Health, Western Australia

Biosecurity research reports

Fluoroacetate, the active ingredient of 1080, occurs naturally in toxic plants in Australia, South Africa, and South America. Manufactured I080 underpins most vertebrate pest control programs in Australia and New Zealand. Fluoroacetate occurs naturally in about 40 plant species in Australia with most of these plants restricted to the south-west of WA.

I080 was introduced to rabbit control programs in the early 1950s and therefore has a long history of proven effectiveness and safety in Australia. There have been few repo1ted problems associated with human safety, environmental persistence, bioaccumulation or impact on populations of non-target species.

In particular, I080 baits …

The Southern African Regional Science Initiative (Safari 2000): Overview Of The Dry Season Field Campaign, R. J. Swap, H. J. Annegarn, J. T. Suttles, J. Haywood, M. C. Helmlinger, C. Hely, Peter V. Hobbs, B. N. Holben, J. Ji, M. D. King, T. Landmann, W. Maenhaut, L. Otter, B. Pak, S. J. Piketh, S. Platnick, J. Privette, D. Roy, A. M. Thompson, Darold E. Ward, Robert J. Yokelson

Chemistry and Biochemistry Faculty Publications

The Southern African Regional Science Initiative (SAFARI 2000) is an international science project investigating the earth-atmosphere-human system in southern Africa. The programme was conducted over a two-year period from March 1999 to March 2001. The dry season field campaign (August-September 2000) was the most intensive activity and involved over 200 scientists from eighteen countries. The main objectives were to characterize and quantify biogenic, pyrogenic and anthropogenic aerosol and trace gas emissions and their transport and transformations in the atmosphere, and to validate NASA's Earth Observing System's satellite Terra within a scientific context. Five aircraft - two South African Weather Service …

Production Of A Monoclonal Antibody Against Benzo[Α]Pyrene Diol Epoxide Dna Adducts, Brian Peden Austin

Chemistry & Biochemistry Theses & Dissertations

Benzo[α]pyrene is a ubiquitous pollutant produced from the incomplete combustion of organic material such as fossil fuels. It is found in the workplace, urban air, drinking water, and the food supply. Recently, it has been proposed that benzo[α]pyrene may be the causative agent in the formation of lung adenocarcinomas among some Taiwanese women exposed to cooking oil fumes without adequate ventilation. In this study, calf thymus DNA was modified in vitro with benzo[α]pyrene-diol epoxide (BPDE) to a level consistent with that found in biological samples. This DNA of low modification was used as an immunogen in the production of a …

Familial Als-Associated Mutations Decrease The Thermal Stability Of Distinctly Metallated Species Of Human Copper/Zinc Superoxide Dismutase, Daryl K. Eggers, J. A. Rodriguez, J. S. Valentine, J. A. Roe, A. Tiwari, R. H. Brown, L. J. Hayward

Faculty Publications, Chemistry

We report the thermal stability of wild type (WT) and 14 different variants of human copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis (FALS). Multiple endothermic unfolding transitions were observed by differential scanning calorimetry for partially metallated SOD1 enzymes isolated from a baculovirus system. We correlated the metal ion contents of SOD1 variants with the occurrence of distinct melting transitions. Altered thermal stability upon reduction of copper with dithionite identified transitions resulting from the unfolding of copper-containing SOD1 species. We demonstrated that copper or zinc binding to a subset of “WT-like” FALS mutants (A4V, L38V, G41S, G72S, D76Y, …