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https://www.readbyqxmd.com/read/28190397/when-good-goes-awry-the-aggregation-of-protein-therapeutics
#1
Jennifer M Redington, Leonid Breydo, Vladimir N Uversky
Protein therapeutics are playing an increasingly important role in treatment of a variety of human diseases. However, like the rest of proteins, they are susceptible to aggregation. Aggregation of proteinaceous pharmaceuticals can cause a loss of efficacy and, potentially, cytotoxicity and an immunogenic response. This review describes various ways protein therapeutics aggregate and a variety of approaches taken to prevent or minimize this process.
February 9, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28178192/structure-and-conformational-properties-of-d-glucose-d-galactose-binding-protein-in-crowded-milieu
#2
Alexander V Fonin, Sergey A Silonov, Asiya K Sitdikova, Irina M Kuznetsova, Vladimir N Uversky, Konstantin K Turoverov
Conformational changes of d-glucose/d-galactose-binding protein (GGBP) were studied under molecular crowding conditions modeled by concentrated solutions of polyethylene glycols (PEG-12000, PEG-4000, and PEG-600), Ficoll-70, and Dextran-70, addition of which induced noticeable structural changes in the GGBP molecule. All PEGs promoted compaction of GGBP and lead to the increase in ordering of its structure. Concentrated solutions of PEG-12000 and PEG-4000 caused GGBP aggregation. Although Ficoll-70 and Dextran-70 also promoted increase in the GGBP ordering, the structural outputs were different for different crowders...
February 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28150000/effects-of-the-hofmeister-series-of-sodium-salts-on-the-solvent-properties-of-water
#3
L A Ferreira, V N Uversky, B Y Zaslavsky
The solvent features of water (solvent dipolarity/polarizability, π*, hydrogen bond donor acidity, α, and hydrogen bond acceptor basicity, β) were examined in aqueous solutions of Na2SO4, NaF, CH3COONa, NaCl, NaBr, NaI, and NaClO4 at concentrations of each salt from 0 to 1.0 M (up to 2.0 M for NaClO4). The solvent features of water in solutions of different concentrations for each salt were found to be linearly related as π* = z + aα + bβ. The coefficients of this relationship were suggested to represent the signature of the salt effect on the solvent features of water...
February 2, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28109327/effects-of-intrinsic-and-extrinsic-factors-on-aggregation-of-physiologically-important-intrinsically-disordered-proteins
#4
L Breydo, J M Redington, V N Uversky
Misfolding and aggregation of proteins and peptides play an important role in a number of diseases as well as in many physiological processes. Many of the proteins that misfold and aggregate in vivo are intrinsically disordered. Protein aggregation is a complex multistep process, and aggregates can significantly differ in morphology, structure, stability, cytotoxicity, and self-propagation ability. The aggregation process is influenced by both intrinsic (e.g., mutations and expression levels) and extrinsic (e...
2017: International Review of Cell and Molecular Biology
https://www.readbyqxmd.com/read/28098335/not-an-exception-to-the-rule-the-functional-significance-of-intrinsically-disordered-protein-regions-in-enzymes
#5
Shelly DeForte, Vladimir N Uversky
Intrinsically disordered protein regions (IDPRs) are remarkably common and have unique and important biological functions. Enzymes have long been considered an exception to the rule of protein intrinsic disorder due to the structural requirements for catalysis. Although functionally significant IDPRs have been described in several enzymes, there has been no study quantifying the extent of this phenomenon. We have conducted a multilevel computational analysis of missing regions in X-ray crystal structures in the PDB and predicted disorder in 66 representative proteomes...
January 18, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28004021/data-on-evolution-of-intrinsically-disordered-regions-of-the-human-kinome-and-contribution-of-fak1-idrs-to-cytoskeletal-remodeling
#6
Jaymin J Kathiriya, Ravi Ramesh Pathak, Alexandr Bezginov, Bin Xue, Vladimir N Uversky, Elisabeth R M Tillier, Vrushank Davé
We present data on the evolution of intrinsically disordered regions (IDRs) taking into account the entire human protein kinome. The evolutionary data of the IDRs with respect to the kinase domains (KDs) and kinases as a whole protein (WP) are reported. Further, we have reported its post translational modifications of FAK1 IDRs and their contribution to the cytoskeletal remodeling. We also report the data to build a protein-protein interaction (PPI) network of primary and secondary FAK1-interacting hybrid proteins...
February 2017: Data in Brief
https://www.readbyqxmd.com/read/27965415/disprot-7-0-a-major-update-of-the-database-of-disordered-proteins
#7
Damiano Piovesan, Francesco Tabaro, Ivan Mičetić, Marco Necci, Federica Quaglia, Christopher J Oldfield, Maria Cristina Aspromonte, Norman E Davey, Radoslav Davidović, Zsuzsanna Dosztányi, Arne Elofsson, Alessandra Gasparini, András Hatos, Andrey V Kajava, Lajos Kalmar, Emanuela Leonardi, Tamas Lazar, Sandra Macedo-Ribeiro, Mauricio Macossay-Castillo, Attila Meszaros, Giovanni Minervini, Nikoletta Murvai, Jordi Pujols, Daniel B Roche, Edoardo Salladini, Eva Schad, Antoine Schramm, Beata Szabo, Agnes Tantos, Fiorella Tonello, Konstantinos D Tsirigos, Nevena Veljković, Salvador Ventura, Wim Vranken, Per Warholm, Vladimir N Uversky, A Keith Dunker, Sonia Longhi, Peter Tompa, Silvio C E Tosatto
No abstract text is available yet for this article.
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27964700/parvalbumin-as-a-pleomorphic-protein
#8
Eugene A Permyakov, Vladimir N Uversky, Sergei E Permyakov
Parvalbumin (PA) is a classical small, mostly cytosolic Ca2+-binding protein of the EF-hand superfamily expressed in vertebrates in a tissue- and cell-specific manner, serving as a magnesium/calcium buffer. In the last decade novel data were published on structural peculiarities of PA, likely affecting its functionality. This review sums up these findings and discusses their potential physiological significance.
December 13, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27936190/two-isoforms-of-yersinia-pestis-plasminogen-activator-pla-intraspecies-distribution-intrinsic-disorder-propensity-and-contribution-to-virulence
#9
Svetlana V Dentovskaya, Mikhail E Platonov, Tat'yana E Svetoch, Pavel Kh Kopylov, Tat'yana I Kombarova, Sergey A Ivanov, Rima Z Shaikhutdinova, Lyubov' V Kolombet, Sadhana Chauhan, Vitaly G Ablamunits, Vladimir L Motin, Vladimir N Uversky, Andrey P Anisimov
It has been shown previously that several endemic Y. pestis isolates with limited virulence contained the I259 isoform of the outer membrane protease Pla, while the epidemic highly virulent strains possessed only the T259 Pla isoform. Our sequence analysis of the pla gene from 118 Y. pestis subsp. microtus strains revealed that the I259 isoform was present exclusively in the endemic strains providing a convictive evidence of more ancestral origin of this isoform. Analysis of the effects of the I259T polymorphism on the intrinsic disorder propensity of Pla revealed that the I259T mutation slightly increases the intrinsic disorder propensity of the C-terminal tail of Pla and makes this protein slightly more prone for disorder-based protein-protein interactions, suggesting that the T259 Pla could be functionally more active than the I259 Pla...
2016: PloS One
https://www.readbyqxmd.com/read/27928941/molecular-dynamics-analysis-of-the-structural-and-dynamic-properties-of-the-functionally-enhanced-hepta-variant-of-mouse-5-aminolevulinate-synthase
#10
Insung Na, Shelly DeForte, Bosko M Stojanovski, Gloria C Ferreira, Vladimir N Uversky
Heme biosynthesis, a complex, multistage, and tightly controlled process, starts with 5-aminolevulinate (ALA) production, which, in metazoa and certain bacteria, is a reaction catalyzed by 5-aminolevulinate synthase (ALAS), a pyridoxal 5'-phosphate (PLP)-dependent enzyme. Functional aberrations in ALAS are associated with several human diseases. ALAS can adopt open and closed conformations, with segmental rearrangements of a C-terminal, 16-amino acid loop and an α-helix regulating accessibility to the ALAS active site...
December 8, 2016: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/27916836/expression-purification-and-characterization-of-interleukin-11-orthologues
#11
Andrei S Sokolov, Alexei S Kazakov, Valery V Solovyev, Ramis G Ismailov, Vladimir N Uversky, Yulia S Lapteva, Roman V Mikhailov, Ekaterina V Pavlova, Iana O Terletskaya, Ludmila V Ermolina, Sergei E Permyakov, Eugene A Permyakov
Interleukin-11 (IL-11) is a multifunctional cytokine implicated in several normal and pathological processes. The decoding of IL-11 function and development of IL-11-targeted drugs dictate the use of laboratory animals and need of the better understanding of species specificity of IL-11 signaling. Here, we present a method for the recombinant interleukin-11 (rIL-11) production from the important model animals, mouse and macaque. The purified mouse and macaque rIL-11 interact with extracellular domain of human IL-11 receptor subunit α and activate STAT3 signaling in HEK293 cells co-expressing human IL-11 receptors with efficacies resembling those of human rIL-11...
November 29, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27899601/disprot-7-0-a-major-update-of-the-database-of-disordered-proteins
#12
Damiano Piovesan, Francesco Tabaro, Ivan Mičetić, Marco Necci, Federica Quaglia, Christopher J Oldfield, Maria Cristina Aspromonte, Norman E Davey, Radoslav Davidović, Zsuzsanna Dosztányi, Arne Elofsson, Alessandra Gasparini, András Hatos, Andrey V Kajava, Lajos Kalmar, Emanuela Leonardi, Tamas Lazar, Sandra Macedo-Ribeiro, Mauricio Macossay-Castillo, Attila Meszaros, Giovanni Minervini, Nikoletta Murvai, Jordi Pujols, Daniel B Roche, Edoardo Salladini, Eva Schad, Antoine Schramm, Beata Szabo, Agnes Tantos, Fiorella Tonello, Konstantinos D Tsirigos, Nevena Veljković, Salvador Ventura, Wim Vranken, Per Warholm, Vladimir N Uversky, A Keith Dunker, Sonia Longhi, Peter Tompa, Silvio C E Tosatto
The Database of Protein Disorder (DisProt, URL: www.disprot.org) has been significantly updated and upgraded since its last major renewal in 2007. The current release holds information on more than 800 entries of IDPs/IDRs, i.e. intrinsically disordered proteins or regions that exist and function without a well-defined three-dimensional structure. We have re-curated previous entries to purge DisProt from conflicting cases, and also upgraded the functional classification scheme to reflect continuous advance in the field in the past 10 years or so...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27867910/intrinsically-disordered-side-of-the-zika-virus-proteome
#13
Rajanish Giri, Deepak Kumar, Nitin Sharma, Vladimir N Uversky
Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs) provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766)...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27854033/comparative-analysis-of-the-antiviral-activity-of-camel-bovine-and-human-lactoperoxidases-against-herpes-simplex-virus-type-1
#14
Esmail M El-Fakharany, Vladimir N Uversky, Elrashdy M Redwan
Lactoperoxidase is a milk hemoprotein that acts as a non-immunoglobulin protective protein and shows strong antimicrobial activity. Bovine milk contains about 15 and 7 times higher levels of lactoperoxidase than human colustrum and camel milk, respectively. Human, bovine, and camel lactoperoxidases (hLPO, bLPO, and cLPO, respectively) were purified as homogeneous samples with specific activities of 4.2, 61.3, and 8.7 u/mg, respectively. The optimal working pH was 7.5 (hLPO and bLPO) and 6.5 (cLPO), whereas the optimal working temperature for these proteins was 40 °C...
November 16, 2016: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/27834926/p53-proteoforms-and-intrinsic-disorder-an-illustration-of-the-protein-structure-function-continuum-concept
#15
REVIEW
Vladimir N Uversky
Although it is one of the most studied proteins, p53 continues to be an enigma. This protein has numerous biological functions, possesses intrinsically disordered regions crucial for its functionality, can form both homo-tetramers and isoform-based hetero-tetramers, and is able to interact with many binding partners. It contains numerous posttranslational modifications, has several isoforms generated by alternative splicing, alternative promoter usage or alternative initiation of translation, and is commonly mutated in different cancers...
November 10, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27834141/in-vitro-exploration-of-the-anti-hcv-potential-of-the-synthetic-spacer-peptides-derived-from-human-bovine-and-camel-lactoferrins
#16
Abdulgader H Albar, Esmail M El-Fakharany, Hussein A Almehdar, Vladimir N Uversky, Elrashdy M Redwan
Chronic liver disease is often associated with the infection by hepatitis C virus (HCV), which is an enveloped RNA virus belonging to the Flaviviridae family. Many studies found that milk proteins, such as lactoferrin, might have profound antiviral activity against HCV. Various secretory fluids ranging from milk, to tears, saliva, and nasal secretion, and to bile and pancreatic juice, as well as neutrophils, mucosal surfaces, and blood contain a widely spread multifunctional glycoprotein, lactoferrin (Lf), structure of which can be depicted as two homologous domains connected by the short spacer peptide...
November 11, 2016: Protein and Peptide Letters
https://www.readbyqxmd.com/read/27833947/erythropoietin-and-co-intrinsic-structure-and-functional-disorder
#17
REVIEW
Vladimir N Uversky, Elrashdy M Redwan
Erythropoietin (Epo) is a heavily glycosylated protein, with its main function being related to erythropoiesis, where it controls red blood cell production via interaction with the Epo receptor (EpoR). It also plays a number of important roles in various hormonal, growth factor, and cytokine pathways. These roles are defined by Epo partners, such as the homodimeric (EpoR)2 receptor, the heterodimeric EpoR/βCR receptor and hypoxia inducing factor (HIF). Although the main structural features of both Epo and EpoR are conserved in vertebrates, the secretion sites of Epo in mammals are different from those in other vertebrates...
December 20, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27824362/electronegativity-and-intrinsic-disorder-of-preeclampsia-related-proteins
#18
Carlos Polanco, Jorge Alberto Castañón-González, Vladimir N Uversky, Thomas Buhse, José Lino Samaniego Mendoza, Juan J Calva
Preeclampsia, hemorrhage, and infection are the leading causes of maternal death in underdeveloped countries. Since several proteins associated with preeclampsia are known, we conducted a computational study which evaluated the commonness and potential functionality of intrinsic disorder of these proteins and also made an attempt to characterize their origin. The origin of the preeclampsia-related proteins was assessed with a supervised technique, a Polarity Index Method (PIM), which evaluates the electronegativity of proteins based solely on their sequence...
November 7, 2016: Acta Biochimica Polonica
https://www.readbyqxmd.com/read/27804860/highly-disordered-proteins-in-prostate-cancer
#19
Vladimir N Uversky, Insung Na, Kevin S Landau, Ryan O Schenk O Schenk
Prostate cancer is one of the major threats to the man's health. There are several mechanisms of the prostate cancer development characterized by the involvement of various androgen-related and androgen-unrelated factors in prostate cancer pathogenesis and in the metastatic carcinogenesis of prostate. In all these processes, proteins play various important roles, and the KEGG database has information on 88 human proteins experimentally shown to be involved in prostate cancer. It is known that many proteins associated with different human maladies are intrinsically disordered (i...
October 28, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27804859/intrinsic-disorder-in-male-sex-determination-disorderedness-of-proteins-from-the-sry-transcriptional-network
#20
Jean Merone, Onyekahi Nwogu, Jennifer M Redington, Vladimir N Uversky
Sex differentiation is a complex process where sexually indifferent embryo progressively acquires male or female characteristics via tightly controlled, perfectly timed, and sophisticatedly intertwined chain of events. This process is controlled and regulated by a set of specific proteins, with one of the first steps in sex differentiation being the activation of the Y-chromosomal Sry gene (sex-determining region Y) in males that acts as a switch from undifferentiated gonad somatic cells to testis development...
October 28, 2016: Current Protein & Peptide Science
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