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https://www.readbyqxmd.com/read/27899601/disprot-7-0-a-major-update-of-the-database-of-disordered-proteins
#1
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...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27867910/intrinsically-disordered-side-of-the-zika-virus-proteome
#2
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
#3
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
#4
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
#5
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
#6
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...
November 11, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27824362/electronegativity-and-intrinsic-disorder-of-preeclampsia-related-proteins
#7
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
#8
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
#9
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
https://www.readbyqxmd.com/read/27801849/peculiarities-of-the-super-folder-gfp-folding-in-a-crowded-milieu
#10
Olesya V Stepanenko, Olga V Stepanenko, Irina M Kuznetsova, Vladimir N Uversky, Konstantin K Turoverov
The natural cellular milieu is crowded by large quantities of various biological macromolecules. This complex environment is characterized by a limited amount of unoccupied space, limited amounts of free water, and changed solvent properties. Obviously, such a tightly packed cellular environment is poorly mimicked by traditional physiological conditions, where low concentrations of a protein of interest are analyzed in slightly salted aqueous solutions. An alternative is given by the use of a model crowded milieu, where a protein of interest is immersed in a solution containing high concentrations of various polymers that serve as model crowding agents...
October 28, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27787828/prediction-of-disordered-rna-dna-and-protein-binding-regions-using-disordpbind
#11
Zhenling Peng, Chen Wang, Vladimir N Uversky, Lukasz Kurgan
Intrinsically disordered proteins and regions (IDPs and IDRs) are involved in a wide range of cellular functions and they often facilitate interactions with RNAs, DNAs, and proteins. Although many computational methods can predict IDPs and IDRs in protein sequences, only a few methods predict their functions and these functions primarily concern protein binding. We describe how to use the first computational method DisoRDPbind for high-throughput prediction of multiple functions of disordered regions. Our method predicts the RNA-, DNA-, and protein-binding residues located in IDRs in the input protein sequences...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27787825/how-to-predict-disorder-in-a-protein-of-interest
#12
Vladimir N Uversky
Currently available computational tools, which are many, provide a researcher with the multitude of options for prediction of intrinsic disorder in a protein of interest and for finding at least some of its disorder-based functions. This chapter provides a highly subjective guideline on how not to be lost in the "dark forest" of available tools for the analysis of intrinsic disorder. By no means it gives a unique pathway through this forest, but simply presents some of the tools the author uses in his everyday research...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27751851/the-unfolding-pathways-of-the-native-and-molten-globule-states-of-5-aminolevulinate-synthase
#13
Bosko M Stojanovski, Leonid Breydo, Vladimir N Uversky, Gloria C Ferreira
In this communication, we report the equilibrium and kinetic properties of the unfolding pathways of the native (pH 7.5) and alkaline molten globule (pH 10.5) states of the pyridoxal 5'-phosphate (PLP)-dependent enzyme 5-aminolevulinate synthase (ALAS). The stability of the molten globule state is adversely affected by thermal- and guanidine hydrochloride (GuHCl)-induced denaturation, and the equilibrium unfolding pathways, irrespective of pH, cannot be described with simple two-state models. Rapid kinetic measurements, in the presence of denaturing GuHCl concentrations, reveal that at pH 10...
October 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27718363/structural-pliability-adjacent-to-the-kinase-domain-highlights-contribution-of-fak1-idrs-to-cytoskeletal-remodeling
#14
Jaymin J Kathiriya, Ravi Ramesh Pathak, Alexandr Bezginov, Bin Xue, Vladimir N Uversky, Elisabeth R M Tillier, Vrushank Davé
Therapeutic protein kinase inhibitors are designed on the basis of kinase structures. Here, we define intrinsically disordered regions (IDRs) in structurally hybrid kinases. We reveal that 65% of kinases have an IDR adjacent to their kinase domain (KD). These IDRs are evolutionarily more conserved than IDRs distant to KDs. Strikingly, 36 kinases have adjacent IDRs extending into their KDs, defining a unique structural and functional subset of the kinome. Functional network analysis of this subset of the kinome uncovered FAK1 as topologically the most connected hub kinase...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27718356/a-widely-employed-germ-cell-marker-is-an-ancient-disordered-protein-with-reproductive-functions-in-diverse-eukaryotes
#15
Michelle A Carmell, Gregoriy A Dokshin, Helen Skaletsky, Yueh-Chiang Hu, Josien C van Wolfswinkel, Kyomi J Igarashi, Daniel W Bellott, Michael Nefedov, Peter W Reddien, George C Enders, Vladimir N Uversky, Craig C Mello, David C Page
The advent of sexual reproduction and the evolution of a dedicated germline in multicellular organisms are critical landmarks in eukaryotic evolution. We report an ancient family of GCNA (germ cell nuclear antigen) proteins that arose in the earliest eukaryotes, and feature a rapidly evolving intrinsically disordered region (IDR). Phylogenetic analysis reveals that GCNA proteins emerged before the major eukaryotic lineages diverged; GCNA predates the origin of a dedicated germline by a billion years. Gcna gene expression is enriched in reproductive cells across eukarya - either just prior to or during meiosis in single-celled eukaryotes, and in stem cells and germ cells of diverse multicellular animals...
October 8, 2016: ELife
https://www.readbyqxmd.com/read/27714063/analysis-of-the-distribution-of-organic-compounds-and-drugs-between-biological-tissues-in-the-framework-of-solute-partitioning-in-aqueous-two-phase-systems
#16
Luisa A Ferreira, Vladimir N Uversky, Boris Y Zaslavsky
Partition coefficients of non-ionic essentially nonpolar compounds between air and rat biological tissues and between blood and other tissues were examined and found to be linearly interrelated according to the previously established equation for partition coefficients of solutes in aqueous two-phase systems: log Kblood-tissue-1 = k0 + k1 log Kblood-tissue-2 + k2 log Kblood-tissue-3, where k0, k1, and k2 are constants. Analysis of partition coefficients of amphiphilic and ionizable drugs between blood and different tissues in rats in vivo showed that the above relationship holds for the blood-tissue partition coefficients of these compounds as well...
September 28, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27671864/challenging-drug-target-for-parkinson-s-disease-pathological-complex-of-the-chameleon-tppp-p25-and-alpha-synuclein-proteins
#17
Tibor Szénási, Judit Oláh, Adél Szabó, Sándor Szunyogh, András Láng, András Perczel, Attila Lehotzky, Vladimir N Uversky, Judit Ovádi
The hallmarks of Parkinson's disease and other synucleinopathies, Tubulin Polymerization Promoting Protein (TPPP/p25) and α-synuclein (SYN) have two key features: they are disordered and co-enriched/co-localized in brain inclusions. These Neomorphic Moonlighting Proteins display both physiological and pathological functions due to their interactions with distinct partners. To achieve the selective targeting of the pathological TPPP/p25-SYN but not the physiological TPPP/p25-tubulin complex, their interfaces were identified as a specific innovative strategy for the development of anti-Parkinson drugs...
September 24, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27663889/what-are-the-structural-features-that-drive-partitioning-of-proteins-in-aqueous-two-phase-systems
#18
Zhonghua Wu, Gang Hu, Kui Wang, Boris Yu Zaslavsky, Lukasz Kurgan, Vladimir N Uversky
Protein partitioning in aqueous two-phase systems (ATPSs) represents a convenient, inexpensive, and easy to scale-up protein separation technique. Since partition behavior of a protein dramatically depends on an ATPS composition, it would be highly beneficial to have reliable means for (even qualitative) prediction of partitioning of a target protein under different conditions. Our aim was to understand which structural features of proteins contribute to partitioning of a query protein in a given ATPS. We undertook a systematic empirical analysis of relations between 57 numerical structural descriptors derived from the corresponding amino acid sequences and crystal structures of 10 well-characterized proteins and the partition behavior of these proteins in 29 different ATPSs...
September 24, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27645710/nickel-impact-on-human-health-an-intrinsic-disorder-perspective
#19
Barbara Zambelli, Vladimir N Uversky, Stefano Ciurli
The interplay of the presence of nickel and protein disorder in processes affecting human health is the focus of the present review. Many systems involving nickel as either a cofactor or as a toxic contaminant are characterized by large disorder. The role of nickel in the biochemistry of bacterial enzymes is discussed here, covering both the beneficial effects of nickel in the human microbiota as well as the role of nickel-depending bacteria in human pathogenesis. In addition, the hazardous health effects caused by nickel exposure to humans, namely nickel-induced carcinogenesis and allergy, are triggered by non-specific interactions of nickel with macromolecules and formation of reactive compounds that mediate cellular damage...
December 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27639966/substitutions-of-amino-acids-with-large-number-of-contacts-in-the-native-state-have-no-effect-on-the-rates-of-protein-folding
#20
Bogdan S Melnik, Galina S Nagibina, Anatoly S Glukhov, Tatiana N Melnik, Vladimir N Uversky
Various effects of amino acid substitutions on properties of globular proteins have been described in a large number of research papers. Nevertheless, no definite "rule" has been formulated as of yet that could be used by experimentalists to introduce desirable changes in the properties of proteins. Herein we attempt to establish such a "rule". To this end, a hypothesis is proposed on the effects of substitutions of hydrophobic residues with large number of contacts on free energies of different states of a globular protein...
December 2016: Biochimica et Biophysica Acta
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