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Latest advancement of omics technologies allows in-depth characterization of venom compositions. In the present work we present a proteomic study of two snake venoms of the genus Naja i.e., Naja naja (black cobra) and Naja oxiana (brown cobra) of Pakistani origin. The present study has shown that these snake venoms consist of a highly diversified proteome. Furthermore, the data also revealed variation among closely related species. High throughput mass spectrometric analysis of the venom proteome allowed to identify for the N. naja venom 34 protein families and for the N. oxiana 24 protein families. The comparative evaluation of the two venoms showed that N. naja consists of a more complex venom proteome than N. oxiana venom. Analysis also showed N-terminal acetylation (N-ace) of a few proteins in both venoms. To the best of our knowledge, this is the first study revealing this posttranslational modification in snake venom. N-ace can shed light on the mechanism of regulation of venom proteins inside the venom gland. Furthermore, our data showed the presence of other body proteins, e.g., ankyrin repeats, leucine repeats, zinc finger, cobra serum albumin, transferrin, insulin, deoxyribonuclease-2-alpha, and other regulatory proteins in these venoms. Interestingly, our data identified Ras-GTpase type of proteins, which indicate the presence of extracellular vesicles in the venom. The data can support the production of distinct and specific anti-venoms and also allow a better understanding of the envenomation and mechanism of distribution of toxins. Data are available via ProteomeXchange with identifier PXD018726.
Aisha Manuwar; Benjamin Dreyer; Andreas Böhmert; Anwar Ullah; Zia Mughal; Ahmed Akrem; Syed Abid Ali; Hartmut Schlüter; Christian Betzel. Proteomic Investigations of Two Pakistani Naja Snake Venoms Species Unravel the Venom Complexity, Posttranslational Modifications, and Presence of Extracellular Vesicles. Toxins 2020, 12, 669 .
AMA StyleAisha Manuwar, Benjamin Dreyer, Andreas Böhmert, Anwar Ullah, Zia Mughal, Ahmed Akrem, Syed Abid Ali, Hartmut Schlüter, Christian Betzel. Proteomic Investigations of Two Pakistani Naja Snake Venoms Species Unravel the Venom Complexity, Posttranslational Modifications, and Presence of Extracellular Vesicles. Toxins. 2020; 12 (11):669.
Chicago/Turabian StyleAisha Manuwar; Benjamin Dreyer; Andreas Böhmert; Anwar Ullah; Zia Mughal; Ahmed Akrem; Syed Abid Ali; Hartmut Schlüter; Christian Betzel. 2020. "Proteomic Investigations of Two Pakistani Naja Snake Venoms Species Unravel the Venom Complexity, Posttranslational Modifications, and Presence of Extracellular Vesicles." Toxins 12, no. 11: 669.
Snake venom L-amino acid oxidases (SV-LAAOs) are the least studied venom enzymes. These enzymes catalyze the stereospecific oxidation of an L-amino acid to their corresponding α-keto acid with the liberation of hydrogen peroxide (H2O2) and ammonia (NH3). They display various pathological and physiological activities including induction of apoptosis, edema, platelet aggregation/inhibition, hemorrhagic, and anticoagulant activities. They also show antibacterial, antiviral and leishmanicidal activity and have been used as therapeutic agents in some disease conditions like cancer and anti-HIV drugs. Although the crystal structures of six SV-LAAOs are present in the Protein Data Bank (PDB), there is no single article that describes all of them in particular. To better understand their structural properties and correlate it with their function, the current work describes structure characterization, structure-based mechanism of catalysis, inhibition and substrate specificity of SV-LAAOs. Sequence analysis indicates a high sequence identity (>84%) among SV-LAAOs, comparatively lower sequence identity with Pig kidney D-amino acid oxidase (<50%) and very low sequence identity (<24%) with bacterial LAAOs, Fugal (L-lysine oxidase), and Zea mays Polyamine oxidase (PAAO). The three-dimensional structure of these enzymes are composed of three-domains, a FAD-binding domain, a substrate-binding domain and a helical domain. The sequence and structural analysis indicate that the amino acid residues in the loops vary in length and composition due to which the surface charge distribution also varies that may impart variable substrate specificity to these enzymes. The active site cavity volume and its average depth also vary in these enzymes. The inhibition of these enzymes by synthetic inhibitors will lead to the production of more potent antivenoms against snakebite envenomation.
Anwar Ullah. Structure–Function Studies and Mechanism of Action of Snake Venom L-Amino Acid Oxidases. Frontiers in Pharmacology 2020, 11, 110 .
AMA StyleAnwar Ullah. Structure–Function Studies and Mechanism of Action of Snake Venom L-Amino Acid Oxidases. Frontiers in Pharmacology. 2020; 11 ():110.
Chicago/Turabian StyleAnwar Ullah. 2020. "Structure–Function Studies and Mechanism of Action of Snake Venom L-Amino Acid Oxidases." Frontiers in Pharmacology 11, no. : 110.
(1) Background. Snake venom phosphodiesterases (SVPDEs) are among the least studied venom enzymes. In envenomation, they display various pathological effects, including induction of hypotension, inhibition of platelet aggregation, edema, and paralysis. Until now, there have been no 3D structural studies of these enzymes, thereby preventing structure–function analysis. To enable such investigations, the present work describes the model-based structural and functional characterization of a phosphodiesterase from Crotalus adamanteus venom, named PDE_Ca. (2) Methods. The PDE_Ca structure model was produced and validated using various software (model building: I-TESSER, MODELLER 9v19, Swiss-Model, and validation tools: PROCHECK, ERRAT, Molecular Dynamic Simulation, and Verif3D). (3) Results. The proposed model of the enzyme indicates that the 3D structure of PDE_Ca comprises four domains, a somatomedin B domain, a somatomedin B-like domain, an ectonucleotide pyrophosphatase domain, and a DNA/RNA non-specific domain. Sequence and structural analyses suggest that differences in length and composition among homologous snake venom sequences may account for their differences in substrate specificity. Other properties that may influence substrate specificity are the average volume and depth of the active site cavity. (4) Conclusion. Sequence comparisons indicate that SVPDEs exhibit high sequence identity but comparatively low identity with mammalian and bacterial PDEs.
Anwar Ullah; Kifayat Ullah; Hamid Ali; Christian Betzel; Shafiq Ur Rehman. The Sequence and a Three-Dimensional Structural Analysis Reveal Substrate Specificity among Snake Venom Phosphodiesterases. Toxins 2019, 11, 625 .
AMA StyleAnwar Ullah, Kifayat Ullah, Hamid Ali, Christian Betzel, Shafiq Ur Rehman. The Sequence and a Three-Dimensional Structural Analysis Reveal Substrate Specificity among Snake Venom Phosphodiesterases. Toxins. 2019; 11 (11):625.
Chicago/Turabian StyleAnwar Ullah; Kifayat Ullah; Hamid Ali; Christian Betzel; Shafiq Ur Rehman. 2019. "The Sequence and a Three-Dimensional Structural Analysis Reveal Substrate Specificity among Snake Venom Phosphodiesterases." Toxins 11, no. 11: 625.
Snake and spider venom is a complex mixture that contains proteins, peptides, and small organic and inorganic compounds. In contrast to spider venom, snake venom proteins are well known both functionally and structurally. This work describes methods for purification and crystallization of snake and spider venom toxins and their three-dimensional structure determination by X-ray crystallography.
Anwar Ullah; Rehana Masood; Zafar Hayat; Ahmed Hafeez. Determining the Structures of the Snake and Spider Toxins by X-Rays. Methods in Molecular Biology 2019, 2068, 163 -172.
AMA StyleAnwar Ullah, Rehana Masood, Zafar Hayat, Ahmed Hafeez. Determining the Structures of the Snake and Spider Toxins by X-Rays. Methods in Molecular Biology. 2019; 2068 ():163-172.
Chicago/Turabian StyleAnwar Ullah; Rehana Masood; Zafar Hayat; Ahmed Hafeez. 2019. "Determining the Structures of the Snake and Spider Toxins by X-Rays." Methods in Molecular Biology 2068, no. : 163-172.
Shahroz Khan; Ijaz Ali; Malik Badshah; Mohammad Qaiser Khan; Zahida Haider; Sajid Ali; Imtiaz Ali Khan; Anwar Ullah. Molecular Epidemiology of Hepatitis C Virus Genotypes Among Chronically Infected Patients in Pakistan. Jundishapur Journal of Microbiology 2019, In Press, 1 .
AMA StyleShahroz Khan, Ijaz Ali, Malik Badshah, Mohammad Qaiser Khan, Zahida Haider, Sajid Ali, Imtiaz Ali Khan, Anwar Ullah. Molecular Epidemiology of Hepatitis C Virus Genotypes Among Chronically Infected Patients in Pakistan. Jundishapur Journal of Microbiology. 2019; In Press (In Press):1.
Chicago/Turabian StyleShahroz Khan; Ijaz Ali; Malik Badshah; Mohammad Qaiser Khan; Zahida Haider; Sajid Ali; Imtiaz Ali Khan; Anwar Ullah. 2019. "Molecular Epidemiology of Hepatitis C Virus Genotypes Among Chronically Infected Patients in Pakistan." Jundishapur Journal of Microbiology In Press, no. In Press: 1.
F Ali; S U Rehman; N M Tareen; K Ullah; A Ullah; T Bibi; S Laghari. EFFECT OF WASTE WATER TREATMENT ON THE GROWTH OF SELECTED LEAFY VEGETABLE PLANTS. Applied Ecology and Environmental Research 2019, 17, 1585 -1597.
AMA StyleF Ali, S U Rehman, N M Tareen, K Ullah, A Ullah, T Bibi, S Laghari. EFFECT OF WASTE WATER TREATMENT ON THE GROWTH OF SELECTED LEAFY VEGETABLE PLANTS. Applied Ecology and Environmental Research. 2019; 17 (2):1585-1597.
Chicago/Turabian StyleF Ali; S U Rehman; N M Tareen; K Ullah; A Ullah; T Bibi; S Laghari. 2019. "EFFECT OF WASTE WATER TREATMENT ON THE GROWTH OF SELECTED LEAFY VEGETABLE PLANTS." Applied Ecology and Environmental Research 17, no. 2: 1585-1597.
The demand for natural medicines has increased because of their limited adverse effects. The aim of study is to explore the antidiabetic potential of isolated steroidal alkaloid from Sarcococca saligna in streptozotocin induced diabetic rats. To determine the antidiabetic activity of steroidal alkaloids, diabetes was induced in rats by injecting streptozotocin intraperitoneally at a dose of 40 mg/Kg. After a week of STZ injection the treatment were started and the 8th day was considered as the 1st day of treatment and up to four weeks the rats were treated with steroidal alkaloids. Animals were divided into five groups, group 1 considered as a control group by receiving normal saline (1 ml/Kg) twice daily and group 2, 3, 4 were treated with active compound sarcovagine-D, saracodine and holaphylline at the dose of 5 mg/Kg subcutaneously twice a day while group 5 was treated with a standard drug glibenclamide at a dose of 1 mg/Kg/day. The result showed that treated group 2 and 4 reduced the glucose level in blood significantly while group 3 showed moderate glucose reduction. The fructosamine level reduced significantly in treating group 4 from the 2nd week of treatment while group 2 and 3 decreased the level significantly in week 4 in diabetic rats. The treated groups showed gradual decreases the glucose level in 1st and 2nd week of oral glucose tolerance test compared to control group. The group receiving holaphylline (4) and sarcovagine-D (2) showed good improvements in blood lipids while the effect of compound on body weight showed less significant improvement. The present study concluded that steroid alkaloids from isolated Sarcococca saligna possess hypoglycemic effect and improve others diabetes associated complications. Together these finding further research is needed using a range of doses to explore the other possible beneficial effects in diabetes mellitus and its molecular mechanism.
Naeem Ullah Jan; Amjad Ali; Bashir Ahmad; Naveed Iqbal; Achyut Adhikari; Inayat- Ur- Rehman; Abid Ali; Safdar Ali; Azra Jahan; Hamid Ali; Ijaz Ali; Anwar Ullah; Syed Ghulam Musharraf. Evaluation of antidiabetic potential of steroidal alkaloid of Sarcococca saligna. Biomedicine & Pharmacotherapy 2018, 100, 461 -466.
AMA StyleNaeem Ullah Jan, Amjad Ali, Bashir Ahmad, Naveed Iqbal, Achyut Adhikari, Inayat- Ur- Rehman, Abid Ali, Safdar Ali, Azra Jahan, Hamid Ali, Ijaz Ali, Anwar Ullah, Syed Ghulam Musharraf. Evaluation of antidiabetic potential of steroidal alkaloid of Sarcococca saligna. Biomedicine & Pharmacotherapy. 2018; 100 ():461-466.
Chicago/Turabian StyleNaeem Ullah Jan; Amjad Ali; Bashir Ahmad; Naveed Iqbal; Achyut Adhikari; Inayat- Ur- Rehman; Abid Ali; Safdar Ali; Azra Jahan; Hamid Ali; Ijaz Ali; Anwar Ullah; Syed Ghulam Musharraf. 2018. "Evaluation of antidiabetic potential of steroidal alkaloid of Sarcococca saligna." Biomedicine & Pharmacotherapy 100, no. : 461-466.
Snake venom thrombin-like enzymes (SVTLEs) constitute the major portion (10–24%) of snake venom and these are the second most abundant enzymes present in the crude venom. During envenomation, these enzymes had shown prominently the various pathological effects, such as disturbance in hemostatic system, fibrinogenolysis, fibrinolysis, platelet aggregation, thrombosis, neurologic disorders, activation of coagulation factors, coagulant, procoagulant etc. These enzymes also been used as a therapeutic agent for the treatment of various diseases such as congestive heart failure, ischemic stroke, thrombotic disorders etc. Although the crystal structures of five SVTLEs are available in the Protein Data Bank (PDB), there is no single article present in the literature that has described all of them. The current work describes the structural aspects, structure-based mechanism of action, processing and inhibition of these enzymes. The sequence analysis indicates that these enzymes show a high sequence identity (57–85%) with each other and low sequence identity with trypsin (36–43%), human alpha-thrombin (29–36%) and other snake venom serine proteinases (57–85%). Three-dimensional structural analysis indicates that the loops surrounding the active site are variable both in amino acids composition and length that may convey variable substrate specificity to these enzymes. The surface charge distributions also vary in these enzymes. Docking analysis with suramin shows that this inhibitor preferably binds to the C-terminal region of these enzymes and causes the destabilization of their three-dimensional structure.
Anwar Ullah; Rehana Masood; Ijaz Ali; Kifayat Ullah; Hamid Ali; Haji Akbar; Christian Betzel. Thrombin-like enzymes from snake venom: Structural characterization and mechanism of action. International Journal of Biological Macromolecules 2018, 114, 788 -811.
AMA StyleAnwar Ullah, Rehana Masood, Ijaz Ali, Kifayat Ullah, Hamid Ali, Haji Akbar, Christian Betzel. Thrombin-like enzymes from snake venom: Structural characterization and mechanism of action. International Journal of Biological Macromolecules. 2018; 114 ():788-811.
Chicago/Turabian StyleAnwar Ullah; Rehana Masood; Ijaz Ali; Kifayat Ullah; Hamid Ali; Haji Akbar; Christian Betzel. 2018. "Thrombin-like enzymes from snake venom: Structural characterization and mechanism of action." International Journal of Biological Macromolecules 114, no. : 788-811.
Spider venoms are complex mixtures of proteins, peptides and small organic and inorganic molecules. Among the proteins, phospholipases D (PLDs) present the major portion, and till now they are the most studied enzymes in spider venom. These PLDs have been divided into two classes, I and II, based on their primary and tertiary structure. Currently, crystal structures of both classes of these enzymes are available in the Protein Data Bank (PDB). Their three-dimensional structure is composed of eight α-helices and eight β-strands forming the ubiquitous fold called triosephosphate isomerase (TIM) barrel. These enzymes use general acid-base catalysis to hydrolyzes their substrate. In this review, we have described the structural features, structure-based mechanisms of catalysis, maturation, and inhibition of these enzymes using the synthetic inhibitor.
Rehana Masood; Kifayat Ullah; Hamid Ali; Ijaz Ali; Christian Betzel; Anwar Ullah. Spider’s venom phospholipases D: A structural review. International Journal of Biological Macromolecules 2018, 107, 1054 -1065.
AMA StyleRehana Masood, Kifayat Ullah, Hamid Ali, Ijaz Ali, Christian Betzel, Anwar Ullah. Spider’s venom phospholipases D: A structural review. International Journal of Biological Macromolecules. 2018; 107 ():1054-1065.
Chicago/Turabian StyleRehana Masood; Kifayat Ullah; Hamid Ali; Ijaz Ali; Christian Betzel; Anwar Ullah. 2018. "Spider’s venom phospholipases D: A structural review." International Journal of Biological Macromolecules 107, no. : 1054-1065.
Synthesis, structural characterization and catalytic application of citrate-stabilized monometallic and bimetallic [email protected] nanoparticles in microbial anti-activities Inayat Ullah,1 Khakemin Khan,2 Muhammad Sohail,3 Kifayat Ullah,4 Anwar Ullah,4 Shabnum Shaheen5 1Lanzhou Center for Tuberculosis Research and Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Peopleâ
Inayat Ullah; Khakemin Khan; Muhammad Sohail; Kifayat Ullah; Anwar Ullah; Shabnum Shaheen. Synthesis, structural characterization and catalytic application of citrate-stabilized monometallic and bimetallic [email protected] nanoparticles in microbial anti-activities. International Journal of Nanomedicine 2017, ume 12, 8735 -8747.
AMA StyleInayat Ullah, Khakemin Khan, Muhammad Sohail, Kifayat Ullah, Anwar Ullah, Shabnum Shaheen. Synthesis, structural characterization and catalytic application of citrate-stabilized monometallic and bimetallic [email protected] nanoparticles in microbial anti-activities. International Journal of Nanomedicine. 2017; ume 12 ():8735-8747.
Chicago/Turabian StyleInayat Ullah; Khakemin Khan; Muhammad Sohail; Kifayat Ullah; Anwar Ullah; Shabnum Shaheen. 2017. "Synthesis, structural characterization and catalytic application of citrate-stabilized monometallic and bimetallic [email protected] nanoparticles in microbial anti-activities." International Journal of Nanomedicine ume 12, no. : 8735-8747.
Rafaela Batista Molás; Marina De Paula-Silva; Rehana Masood; Anwar Ullah; Alexandre Dantas Gimenes; Sonia Maria Oliani. Ac2-26 peptide and serine protease of Bothrops atrox similarly induces angiogenesis without triggering local and systemic inflammation in a murine model of dorsal skinfold chamber. Toxicon 2017, 137, 7 -14.
AMA StyleRafaela Batista Molás, Marina De Paula-Silva, Rehana Masood, Anwar Ullah, Alexandre Dantas Gimenes, Sonia Maria Oliani. Ac2-26 peptide and serine protease of Bothrops atrox similarly induces angiogenesis without triggering local and systemic inflammation in a murine model of dorsal skinfold chamber. Toxicon. 2017; 137 ():7-14.
Chicago/Turabian StyleRafaela Batista Molás; Marina De Paula-Silva; Rehana Masood; Anwar Ullah; Alexandre Dantas Gimenes; Sonia Maria Oliani. 2017. "Ac2-26 peptide and serine protease of Bothrops atrox similarly induces angiogenesis without triggering local and systemic inflammation in a murine model of dorsal skinfold chamber." Toxicon 137, no. : 7-14.
The interaction of flavonoid Quercetin with Phospholipase A2 isolated from snake venom Bothrops brazili (MTX-II) was investigated by fluorescence spectroscopy and molecular modeling. The fluorimetric titrations were conducted at 288, 298 and 308 K and at pH 8.0. Stern-Volmer quenching constant (KSV) and binding constant (Kb) were calculated along with the corresponding thermodynamic parameters ΔG, ΔH and ΔS at 288 and 298 K. From these analysis evidences of complex formation in between MTX-II and QCT are found. Besides that modified Stern-Volmer plot show evidences for two types of intrinsic fluorophores with different accessibilities at 308 K. The mean distance between the donor (MTX-II) and acceptor (QCT) was determined by fluorescence resonance energy transfer (FRET). The optimized structure of QCT was obtained by ab initio calculation, which geometry was performed in its ground states by using DFT/B3LYP functional with 6-311+G (d,p) basis set. The molecular docking analysis show that QCT may be localized at two main clusters, the first is at the dimer interface and the second at the active site like region. The clusters positions and binding energies reinforce the experimental data.
Reetesh Kumar; Icaro P Caruso; Anwar Ullah; Marinonio Lopes Cornelio; Marcelo Andres Fossey; Fatima Pereira De Souza; Raghuvir Krishnaswamy Arni. Exploring the Binding Mechanism of Flavonoid Quercetin to Phospholipase A2: Fluorescence Spectroscopy and Computational Approach. European Journal of Experimental Biology 2017, 07, 1 .
AMA StyleReetesh Kumar, Icaro P Caruso, Anwar Ullah, Marinonio Lopes Cornelio, Marcelo Andres Fossey, Fatima Pereira De Souza, Raghuvir Krishnaswamy Arni. Exploring the Binding Mechanism of Flavonoid Quercetin to Phospholipase A2: Fluorescence Spectroscopy and Computational Approach. European Journal of Experimental Biology. 2017; 07 (05):1.
Chicago/Turabian StyleReetesh Kumar; Icaro P Caruso; Anwar Ullah; Marinonio Lopes Cornelio; Marcelo Andres Fossey; Fatima Pereira De Souza; Raghuvir Krishnaswamy Arni. 2017. "Exploring the Binding Mechanism of Flavonoid Quercetin to Phospholipase A2: Fluorescence Spectroscopy and Computational Approach." European Journal of Experimental Biology 07, no. 05: 1.
The discovery of rapid acting and powerful angiogenic proteins are of significant interest in the treatment of various human disorders associated with insufficient angiogenesis such as ischemia, menorrhagia and delayed wound healing. Snake venoms consist of a mixture of bioactive proteins and polypeptides and are rich sources of pharmacologically important molecules. Serine proteinases are one of the abundant proteins present in Bothrops snake venoms and possess multiple biological functions including the regulation of the blood coagulation cascade. In this study, serine proteinases from Bothrops atrox (B. atrox) and Bothrops brazili (B. brazili) that modulate angiogenesis were purified and characterized. Molecular size exclusion chromatography, affinity chromatography followed by ion exchange chromatography of the serine proteinases indicated molecular masses of around 32 kDa. Serine proteinases from both the species exhibited diverse catalytic activities such as the ability to induce amidolytic, fibrinogenolytic, gelatinolytic activities and also coagulated plasma with a minimal coagulation concentration of 2.4 μg/mL. Serine proteinases facilitated the sprouting of human umbilical vein endothelial cells (HUVEC) in three-dimensional culture systems and induced tubule formation in monolayer culture systems. Serine proteinase stimulated Akt and eNOS phosphorylation in endothelial cells and addition of PI3K inhibitor LY294002 abrogated the effects of serine proteinases on sprout formation of endothelial cells in 3D collagen gels, suggesting that serine proteinase facilitated angiogenesis was mediated by PI3K/eNOS signaling axis. We also show in agarose plug assays using a mouse model, serine proteinases from Bothrops venoms significantly enhanced neovascularization. Our data suggests pro-angiogenic activity by the serine proteinases from B. atrox and B. brazili venom and further studies are warranted to explore the therapeutic applications.
Shreesha K. Bhat; Manjunath Joshi; Anwar Ullah; Rehana Masood; Setlur G. Biligiri; Raghuvir K. Arni; Kapaettu Satyamoorthy. Serine proteinases from Bothrops snake venom activates PI3K/Akt mediated angiogenesis. Toxicon 2016, 124, 63 -72.
AMA StyleShreesha K. Bhat, Manjunath Joshi, Anwar Ullah, Rehana Masood, Setlur G. Biligiri, Raghuvir K. Arni, Kapaettu Satyamoorthy. Serine proteinases from Bothrops snake venom activates PI3K/Akt mediated angiogenesis. Toxicon. 2016; 124 ():63-72.
Chicago/Turabian StyleShreesha K. Bhat; Manjunath Joshi; Anwar Ullah; Rehana Masood; Setlur G. Biligiri; Raghuvir K. Arni; Kapaettu Satyamoorthy. 2016. "Serine proteinases from Bothrops snake venom activates PI3K/Akt mediated angiogenesis." Toxicon 124, no. : 63-72.
Loxoscelism refers to the clinical symptoms that develop after brown spider bites. Brown spider venoms contain several phospholipase-D isoforms, which are the main toxins responsible for both the cutaneous and systemic effects of loxoscelism. Understanding of the phospholipase-D catalytic mechanism is crucial for the development of specific treatment that could reverse the toxic effects caused by the spider bite. Based on enzymatic, biological, structural, and thermodynamic tests, we show some features suitable for designing drugs against loxoscelism. Firstly, through molecular docking and molecular dynamics predictions, we found three different molecules (Suramin, Vu0155056, and Vu0359595) that were able to bind the enzyme's catalytic site and interact with catalytically important residues (His12 or His47) and with the Mg2+ co-factor. The binding promoted a decrease in the recombinant brown spider venom phospholipase-D (LiRecDT1) enzymatic activity. Furthermore, the presence of the inhibitors reduced the hemolytic, dermonecrotic, and inflammatory activities of the venom toxin in biological assays. Altogether, these results indicate the mode of action of three different LiRecDT1 inhibitors, which were able to prevent the venom toxic effects. This strengthen the idea of the importance of designing a specific drug to treat the serious clinical symptoms caused by the brown spider bite, a public health problem in several parts of the world, and until now without specific treatment. J. Cell. Biochem. 9999: 1–13, 2016.
Daniele Moreira; Fabio Rogerio de Moraes; Icaro Caruso; Olga Chaim; Andrea Senff-Ribeiro; Anwar Ullah; Luciane Sussuchi da Silva; Jorge Chahine; Raghuvir Arni; Silvio Sanches Veiga. Potential Implications for Designing Drugs Against the Brown Spider Venom Phospholipase-D. Journal of Cellular Biochemistry 2016, 118, 726 -738.
AMA StyleDaniele Moreira, Fabio Rogerio de Moraes, Icaro Caruso, Olga Chaim, Andrea Senff-Ribeiro, Anwar Ullah, Luciane Sussuchi da Silva, Jorge Chahine, Raghuvir Arni, Silvio Sanches Veiga. Potential Implications for Designing Drugs Against the Brown Spider Venom Phospholipase-D. Journal of Cellular Biochemistry. 2016; 118 (4):726-738.
Chicago/Turabian StyleDaniele Moreira; Fabio Rogerio de Moraes; Icaro Caruso; Olga Chaim; Andrea Senff-Ribeiro; Anwar Ullah; Luciane Sussuchi da Silva; Jorge Chahine; Raghuvir Arni; Silvio Sanches Veiga. 2016. "Potential Implications for Designing Drugs Against the Brown Spider Venom Phospholipase-D." Journal of Cellular Biochemistry 118, no. 4: 726-738.
The Arginine Repressor (ArgR) regulates arginine biosynthesis in a number of microorganisms and consists of two domains interlinked by a short peptide; the N-terminal domain is involved in DNA binding and the C-terminal domain binds arginine and forms a hexamer made-up of a dimer of trimers. The crystal structure of the C-terminal domain of ArgR from the pathogenic Corynebacterium pseudotuberculosis determined at 1.9 Å resolution contains a tightly bound tyrosine at the arginine-binding site indicating hitherto unobserved promiscuity. Structural analysis of the binding pocket displays clear molecular adaptations to accommodate tyrosine binding suggesting the possible existence of an alternative regulatory process in this pathogenic bacterium.
Ricardo Barros Mariutti; Anwar Ullah; Gabriela Campos Araujo; Mario Tyago Murakami; Raghuvir Krishnaswamy Arni. Tyrosine binding and promiscuity in the arginine repressor from the pathogenic bacterium Corynebacterium pseudotuberculosis. Biochemical and Biophysical Research Communications 2016, 475, 350 -355.
AMA StyleRicardo Barros Mariutti, Anwar Ullah, Gabriela Campos Araujo, Mario Tyago Murakami, Raghuvir Krishnaswamy Arni. Tyrosine binding and promiscuity in the arginine repressor from the pathogenic bacterium Corynebacterium pseudotuberculosis. Biochemical and Biophysical Research Communications. 2016; 475 (4):350-355.
Chicago/Turabian StyleRicardo Barros Mariutti; Anwar Ullah; Gabriela Campos Araujo; Mario Tyago Murakami; Raghuvir Krishnaswamy Arni. 2016. "Tyrosine binding and promiscuity in the arginine repressor from the pathogenic bacterium Corynebacterium pseudotuberculosis." Biochemical and Biophysical Research Communications 475, no. 4: 350-355.
Southern bean mosaic virus (SBMV) RNA purified from infected plants was used for cloning the viral genome-linked protein (VPg) and was subsequently expressed in Escherichia coli. Circular dichroism (CD), dynamic light scattering (DLS) and saturation transfer difference (STD) by nuclear magnetic resonance (NMR) measurements were employed to determine the degree of monodispersity and to investigate the conformational changes in the absence and presence of trifluoroethanol (TFE) which indicated increased helical content with increasing concentration of TFE. 8-Anilino-1-naphthalenesulfonic acid (ANS) was used as a probe to compare the unfolding regions of the protein before and after addition of TFE. The results indicated that although the TFE concentration influences VPg folding, it does not play a role in nucleotide binding and that the local solvent hydrophobicity causes significant conformational changes
Ricardo Mariutti; Icaro Caruso; Anwar Ullah; F.R. De Morais; D. Rehders; R.K. Arni. Functional expression, monodispersity and conformational changes in the SBMV virus viral VPg on binding TFE. International Journal of Biological Macromolecules 2016, 83, 178 -184.
AMA StyleRicardo Mariutti, Icaro Caruso, Anwar Ullah, F.R. De Morais, D. Rehders, R.K. Arni. Functional expression, monodispersity and conformational changes in the SBMV virus viral VPg on binding TFE. International Journal of Biological Macromolecules. 2016; 83 ():178-184.
Chicago/Turabian StyleRicardo Mariutti; Icaro Caruso; Anwar Ullah; F.R. De Morais; D. Rehders; R.K. Arni. 2016. "Functional expression, monodispersity and conformational changes in the SBMV virus viral VPg on binding TFE." International Journal of Biological Macromolecules 83, no. : 178-184.
2S albumins, the seed storage proteins, are the primary sources of carbon and nitrogen and are involved in plant defense. The mature form of Moringa oleifera (M. oleifera), a chitin binding protein isoform 3-1 (mMo-CBP3-1) a thermostable antifungal, antibacterial, flocculating 2S albumin is widely used for the treatment of water and is potentially interesting for the development of both antifungal drugs and transgenic crops. The crystal structure of mMo-CBP3-1 determined at 1.7 Å resolution demonstrated that it is comprised of two proteolytically processed α-helical chains, stabilized by four disulfide bridges that is stable, resistant to pH changes and has a melting temperature (TM) of approximately 98 °C. The surface arginines and the polyglutamine motif are the key structural factors for the observed flocculating, antibacterial and antifungal activities. This represents the first crystal structure of a 2S albumin and the model of the pro-protein indicates the structural changes that occur upon formation of mMo-CBP3-1 and determines the structural motif and charge distribution patterns for the diverse observed activities.
Anwar Ullah; Ricardo Mariutti; Rehana Masood; Icaro Caruso; Gustavo Henrique Gravatim Costa; Cristhyane Millena de Freita; Camila Santos; Leticia Maria Zanphorlin; Márcia Justino Rossini Mutton; Mario Tyago Murakami; Raghuvir Krishnaswamy Arni. Crystal structure of mature 2S albumin from Moringa oleifera seeds. Biochemical and Biophysical Research Communications 2015, 468, 365 -371.
AMA StyleAnwar Ullah, Ricardo Mariutti, Rehana Masood, Icaro Caruso, Gustavo Henrique Gravatim Costa, Cristhyane Millena de Freita, Camila Santos, Leticia Maria Zanphorlin, Márcia Justino Rossini Mutton, Mario Tyago Murakami, Raghuvir Krishnaswamy Arni. Crystal structure of mature 2S albumin from Moringa oleifera seeds. Biochemical and Biophysical Research Communications. 2015; 468 (1-2):365-371.
Chicago/Turabian StyleAnwar Ullah; Ricardo Mariutti; Rehana Masood; Icaro Caruso; Gustavo Henrique Gravatim Costa; Cristhyane Millena de Freita; Camila Santos; Leticia Maria Zanphorlin; Márcia Justino Rossini Mutton; Mario Tyago Murakami; Raghuvir Krishnaswamy Arni. 2015. "Crystal structure of mature 2S albumin from Moringa oleifera seeds." Biochemical and Biophysical Research Communications 468, no. 1-2: 365-371.
Phospholipases D (PLDs), the major dermonecrotic factors from brown spider venoms, trigger a range of biological reactions both in vitro and in vivo. Despite their clinical relevance in loxoscelism, structural data is restricted to the apo-form of these enzymes, which has been instrumental in understanding the functional differences between the class I and II spider PLDs. The crystal structures of the native class II PLD from Loxosceles intermedia complexed with myo-inositol 1-phosphate and the inactive mutant H12A complexed with fatty acids indicate the existence of a strong ligand-dependent conformation change of the highly conserved aromatic residues, Tyr 223 and Trp225 indicating their roles in substrate binding. These results provided insights into the structural determinants for substrate recognition and binding by class II PLDs.
M.A. Coronado; Anwar Ullah; Luciane Sussuchi da Silva; Daniele Moreira; L. Vuitika; Olga Chaim; S.S. Veiga; Jorge Chahine; M.T. Murakami; R.K. Arni. Structural Insights into Substrate Binding of Brown Spider Venom Class II Phospholipases D. Current Protein & Peptide Science 2015, 16, 768 -774.
AMA StyleM.A. Coronado, Anwar Ullah, Luciane Sussuchi da Silva, Daniele Moreira, L. Vuitika, Olga Chaim, S.S. Veiga, Jorge Chahine, M.T. Murakami, R.K. Arni. Structural Insights into Substrate Binding of Brown Spider Venom Class II Phospholipases D. Current Protein & Peptide Science. 2015; 16 (8):768-774.
Chicago/Turabian StyleM.A. Coronado; Anwar Ullah; Luciane Sussuchi da Silva; Daniele Moreira; L. Vuitika; Olga Chaim; S.S. Veiga; Jorge Chahine; M.T. Murakami; R.K. Arni. 2015. "Structural Insights into Substrate Binding of Brown Spider Venom Class II Phospholipases D." Current Protein & Peptide Science 16, no. 8: 768-774.
Exfoliative toxins are serine proteases secreted by Staphylococcus aureus that are associated with toxin-mediated staphylococcal syndromes. To date, four different serotypes of exfoliative toxins have been identified and 3 of them (ETA, ETB, and ETD) are linked to human infection. Among these toxins, only the ETD structure remained unknown, limiting our understanding of the structural determinants for the functional differentiation between these toxins. We recently identified an ETD-like protein associated to S. aureus strains involved in mild mastitis in sheep. The crystal structure of this ETD-like protein was determined at 1.95 Å resolution and the structural analysis provide insights into the oligomerization, stability and specificity and enabled a comprehensive structural comparison with ETA and ETB. Despite the highly conserved molecular architecture, significant differences in the composition of the loops and in both the N- and C-terminal α-helices seem to define ETD-like specificity. Molecular dynamics simulations indicate that these regions defining ET specificity present different degrees of flexibility and may undergo conformational changes upon substrate recognition and binding. DLS and AUC experiments indicated that the ETD-like is monomeric in solution whereas it is present as a dimer in the asymmetric unit indicating that oligomerization is not related to functional differentiation among these toxins. Differential scanning calorimetry and circular dichroism assays demonstrated an endothermic transition centered at 52 °C, and an exothermic aggregation in temperatures up to 64 °C. All these together provide insights about the mode of action of a toxin often secreted in syndromes that are not associated with either ETA or ETB.
Ricardo Mariutti; Tatiana A.C.B. Souza; Anwar Ullah; Icaro Caruso; Fábio R. de Moraes; Leticia M. Zanphorlin; Natayme R. Tartaglia; Nubia Seyffert; Vasco A. Azevedo; Yves Le Loir; Mário T. Murakami; Raghuvir K. Arni. Crystal structure of Staphylococcus aureus exfoliative toxin D-like protein: Structural basis for the high specificity of exfoliative toxins. Biochemical and Biophysical Research Communications 2015, 467, 171 -177.
AMA StyleRicardo Mariutti, Tatiana A.C.B. Souza, Anwar Ullah, Icaro Caruso, Fábio R. de Moraes, Leticia M. Zanphorlin, Natayme R. Tartaglia, Nubia Seyffert, Vasco A. Azevedo, Yves Le Loir, Mário T. Murakami, Raghuvir K. Arni. Crystal structure of Staphylococcus aureus exfoliative toxin D-like protein: Structural basis for the high specificity of exfoliative toxins. Biochemical and Biophysical Research Communications. 2015; 467 (1):171-177.
Chicago/Turabian StyleRicardo Mariutti; Tatiana A.C.B. Souza; Anwar Ullah; Icaro Caruso; Fábio R. de Moraes; Leticia M. Zanphorlin; Natayme R. Tartaglia; Nubia Seyffert; Vasco A. Azevedo; Yves Le Loir; Mário T. Murakami; Raghuvir K. Arni. 2015. "Crystal structure of Staphylococcus aureus exfoliative toxin D-like protein: Structural basis for the high specificity of exfoliative toxins." Biochemical and Biophysical Research Communications 467, no. 1: 171-177.
Grapevine virus A (GVA), a flexible filament of approximately 800 nm in length is composed of capsid subunits that spontaneously assembles around a positive sense genomic RNA. In addition to encapsidation, plant viruses capsid proteins (CPs) participate in other processes throughout infection and GVA CP is involved in cell-to-cell translocation of the virus. A protocol was developed to obtain low-molecular weight GVA-CP that is not prone to aggregation and spontaneous assembly and this was characterized by circular dichroism and dynamic light scattering. These results indicate the suitably of GVA-CP for X-ray crystallographic and NMR studies that should lead to the elucidation of the first three-dimensional structure of a flexible filamentous virus from the Betaflexiviridae family.
Vinícius S Santana; Ricardo B Mariutti; Raphael J Eberle; Anwar Ullah; Icaro P Caruso; Raghuvir K Arni. Preparation and Characterization of Monomodal Grapevine Virus A Capsid Protein. Protein & Peptide Letters 2015, 22, 712 -718.
AMA StyleVinícius S Santana, Ricardo B Mariutti, Raphael J Eberle, Anwar Ullah, Icaro P Caruso, Raghuvir K Arni. Preparation and Characterization of Monomodal Grapevine Virus A Capsid Protein. Protein & Peptide Letters. 2015; 22 (8):712-718.
Chicago/Turabian StyleVinícius S Santana; Ricardo B Mariutti; Raphael J Eberle; Anwar Ullah; Icaro P Caruso; Raghuvir K Arni. 2015. "Preparation and Characterization of Monomodal Grapevine Virus A Capsid Protein." Protein & Peptide Letters 22, no. 8: 712-718.