Structural Basis For Calmodulin As A Dynamic Calcium Sensor,
2012
Chapman University
Structural Basis For Calmodulin As A Dynamic Calcium Sensor, Miao Zhang, Cameron Abrams, Liping Wang, Anthony Gizzi, Liping He, Ruihe Lin, Yuan Chen, Patrick J. Loll, John M. Pascal, Ji-Fang Zhang
Pharmacy Faculty Articles and Research
Calmodulin is a prototypical and versatile Ca2+ sensor with EF-hands as its high-affinity Ca2+ binding domains. Calmodulin is present in all eukaryotic cells, mediating Ca2+-dependent signaling. Upon binding Ca2+, calmodulin changes its conformation to form complexes with a diverse array of target proteins. Despite a wealth of knowledge on calmodulin, little is known on how target proteins regulate calmodulin’s ability to bind Ca2+. Here, we take advantage of two splice variants of SK2 channels, which are activated by Ca2+-bound calmodulin, but show different sensitivity to Ca2+ for their activation. Protein crystal structures and other experiments show that depending on which …
Selectivity Of The Ubiquitin-Binding Modules,
2012
Chapman University
Selectivity Of The Ubiquitin-Binding Modules, Simin Rahighi, Ivan Dikic
Pharmacy Faculty Articles and Research
Ubiquitin-binding modules are constituents of cellular proteins that mediate the effects of ubiquitylation by making transient, non-covalent interactions with ubiquitin molecules. While some ubiquitin- binding modules bind single ubiquitin moieties, others are selective for specific ubiquitin chains of different linkage types and lengths. In recent years, functions of ubiquitin chains that are polymerized through their Lys or N-terminal Met (i.e. linear chains) residues have been linked to a variety of cellular processes. Selectivity of ubiquitin-binding modules for different ubiquitin chain types appears as a key to the distinct regulatory consequences during protein quality control pathways, receptor endocytosis, gene transcription, signaling …
Genetic Ablation Of Cav1 Differentially Affects Melanoma Tumor Growth And Metastasis In Mice: Role Of Cav1 In Shh Heterotypic Signaling And Transendothelial Migration.,
2012
Thomas Jefferson University
Genetic Ablation Of Cav1 Differentially Affects Melanoma Tumor Growth And Metastasis In Mice: Role Of Cav1 In Shh Heterotypic Signaling And Transendothelial Migration., Franco Capozza, Casey Trimmer, Remedios Castello-Cros, Sanjay Katiyar, Diana Whitaker-Menezes, Antonia Follenzi, Marco Crosariol, Gemma Llaverias, Federica Sotgia, Richard G Pestell, Michael P Lisanti
Department of Cancer Biology Faculty Papers
Both cell-autonomous and non-cell-autonomous factors contribute to tumor growth and metastasis of melanoma. The function of caveolin-1 (Cav1), a multifunctional scaffold protein known to modulate several biologic processes in both normal tissue and cancer, has been recently investigated in melanoma cancer cells, but its role in the melanoma microenvironment remains largely unexplored. Here, we show that orthotopic implantation of B16F10 melanoma cells in the skin of Cav1KO mice increases tumor growth, and co-injection of Cav1-deficient dermal fibroblasts with melanoma cells is sufficient to recapitulate the tumor phenotype observed in Cav1KO mice. Using indirect coculture experiments with fibroblasts and melanoma cells …
The Mechanical Behavior Of Mutant K14-R125p Keratin Bundles And Networks In Neb-1 Keratinocytes,
2012
University of Guelph
The Mechanical Behavior Of Mutant K14-R125p Keratin Bundles And Networks In Neb-1 Keratinocytes, Daniel R. Beriault, Oualid Haddad, John V. Mccuaig, Zachary J. Robinson, David Russell, E. Birgitte Lane, Douglas S. Fudge
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Epidermolysis bullosa simplex (EBS) is an inherited skin-blistering disease that is caused by dominant mutations in the genes for keratin K5 or K14 proteins. While the link between keratin mutations and keratinocyte fragility in EBS patients is clear, the exact biophysical mechanisms underlying cell fragility are not known. In this study, we tested the hypotheses that mutant K14-R125P filaments and/or networks in human keratinocytes are mechanically defective in their response to large-scale deformations. We found that mutant filaments and networks exhibit no obvious defects when subjected to large uniaxial strains and have no negative effects on the ability of human …
Gold Ion–Angiotensin Peptide Interaction By Mass Spectrometry,
2012
Illinois Mathematics and Science Academy
Gold Ion–Angiotensin Peptide Interaction By Mass Spectrometry, Jenny Lee '13, Lasanthi P. Jayathilaka, Shalini Gupta, Jin-Sheng Huang, Bao- Shiang Lee
Student Publications & Research
Stimulated by the interest in developing gold compounds for treating cancer, gold ion– angiotensin peptide interactions are investigated by mass spectrometry. Under the experimental conditions used, the majority of gold ion–angiotensin peptide complexes contain gold in the oxidation states I and III. Both ESI-MS and MALDI-TOF MS detect singly/multiply charged ions for mononuclear/multinuclear gold-attached peptides, which are represented as [peptide+a Au (I)+b Au(III)+(e - a -3b) H]e+, where a,b≥0 and e is charge. ESI-MS data shows singly/multiply charged ions of Au(I)-peptide and Au(III)-peptide complexes. This study reveals that MALDITOF MS mainly detects singly charged Au(I)-peptide complexes, presumably due to the …
Cryo-Em Structure Of The Archaeal 50s Ribosomal Subunit In Complex With Initiation Factor 6 And Implications For Ribosome Evolution,
2012
ETH Zurich
Cryo-Em Structure Of The Archaeal 50s Ribosomal Subunit In Complex With Initiation Factor 6 And Implications For Ribosome Evolution, Basil J. Greber, Daniel Boehringer, Vlatka Godinic-Mikulcic, Ana Crnkovic, Michael Ibba, Ivana Weygand-Durasevic, Nenad Ban
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Translation of mRNA into proteins by the ribosome is universally conserved in all cellular life. The composition and complexity of the translation machinery differ markedly between the three domains of life. Organisms from the domain Archaea show an intermediate level of complexity, sharing several additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter thermautotrophicus in complex with archaeal IF6 at 6.6 Å resolution using cryo-electron microscopy (EM). The …
Roles Of Trna In Cell Wall Biosynthesis,
2012
The Ohio State University
Roles Of Trna In Cell Wall Biosynthesis, Kiley Dare, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Recent research into various aspects of bacterial metabolism such as cell wall and antibiotic synthesis, degradation pathways, cellular stress, and amino acid biosynthesis has elucidated roles of aminoacyl‐transfer ribonucleic acid (aa‐tRNA) outside of translation. Although the two enzyme families responsible for cell wall modifications, aminoacyl‐phosphatidylglycerol synthases (aaPGSs) and Fem, were discovered some time ago, they have recently become of intense interest for their roles in the antimicrobial resistance of pathogenic microorganisms. The addition of positively charged amino acids to phosphatidylglycerol (PG) by aaPGSs neutralizes the lipid bilayer making the bacteria less susceptible to positively charged antimicrobial agents. Fem transferases utilize …
Synthetic Peptides Derived From The Sequence Of A Lasso Peptide Microcin J25 Show Antibacterial Activity,
2012
University of Alberta
Synthetic Peptides Derived From The Sequence Of A Lasso Peptide Microcin J25 Show Antibacterial Activity, Rania Soudy, Liru Wang, Kamaljit Kaur
Pharmacy Faculty Articles and Research
Microcin J25 (MccJ25) is a plasmid-encoded, ribosomally synthesized antibacterial peptide with a unique lasso structure. The lasso structure, produced with the aid of two processing enzymes, provides exceptional stability to MccJ25. We report the synthesis of six peptides (1–6), derived from the MccJ25 sequence, that are designed to form folded conformation by disulfide bond formation and electrostatic or hydrophobic interactions. Two peptides (1 and 6) display good activity against Salmonella newport, and are the first synthetic derivatives of MccJ25 that are bactericidal. Peptide 1 displays potent activity against several Salmonella strains including two …
Linus Pauling: Scientist Of The 20th Century,
2012
Parkland College
Linus Pauling: Scientist Of The 20th Century, Laura Ward
Natural Sciences Student Research Presentations
This poster describes the contributions scientist Linus Pauling made to the fields of chemistry and molecular biology, including his hybridization theory.
N-Myristoylglutamic Acid Derivative Of 3′-Fluoro-3′- Deoxythymidine As An Organogel,
2012
University of Rhode Island
N-Myristoylglutamic Acid Derivative Of 3′-Fluoro-3′- Deoxythymidine As An Organogel, Bhupender S. Chhikara, Rakesh Tiwari, Keykavous Parang
Pharmacy Faculty Articles and Research
Designing microbicidal gels of anti-HIV drugs for local application to prevent HIV infection is a subject of major interest. 3′-Fluoro-3′-deoxythymidine (FLT), a nucleoside reverse transcriptase inhibitor (NRTI), was conjugated with a N-myristoylglutamate scaffold. The conjugate showed gelation at 1% (w/w) in different organic solvents, such as toluene, dichloromethane, and chloroform. The gels were opaque and stable at room temperature. The results indicate that myristoyl glutamate derivative of FLT can form an organogel. The gel could have potential application as a topical anti-HIV microbicidal agent.
Hepatic Immunosuppressive Effects Of Systemically- Administered Novel Dextran-Methylprednisolone Prodrugs With Peptide Linkers In Rats,
2012
Texas Tech University
Hepatic Immunosuppressive Effects Of Systemically- Administered Novel Dextran-Methylprednisolone Prodrugs With Peptide Linkers In Rats, Imam H. Shaik, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar
Pharmacy Faculty Articles and Research
The hepatic immunosuppressive activities of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP1) or five (DMP5) amino acids as linkers were studied in rats. At various times (02 weeks) after intravenous administration of single 5 mg/kg (MP equivalent) doses of each prodrug or MP succinate (MPS), livers were isolated and immunologically stimulated ex vivo with lipopolysaccharide. The concentrations of tumor necrosis factor (TNF)-a in the outlet perfusate were then quantitated to assess immune response. Additionally, the concentrations of DMP1, DMP5, and/or MP were measured in the liver. MPS, DMP5, or DMP1 injections caused a maximum of 48.9%, 63.5%, …
Melatonin Membrane Receptors In Peripheral Tissues: Distribution And Functions,
2012
University of Tennessee
Melatonin Membrane Receptors In Peripheral Tissues: Distribution And Functions, Radomir M. Slominski, Russel J. Reiter, Natalia Schlabritz-Loutsevich, Rennolds S. Ostrom, Andrzej T. Slominski
Pharmacy Faculty Articles and Research
Many of melatonin’s actions are mediated through interaction with the G-protein coupled membrane bound melatonin receptors type 1 and type 2 (MT1 and MT2, respectively) or, indirectly with nuclear orphan receptors from the RORα/RZR family. Melatonin also binds to the quinone reductase II enzyme, previously defined the MT3 receptor. Melatonin receptors are widely distributed in the body; herein we summarize their expression and actions in non-neural tissues. Several controversies still exist regarding, for example, whether melatonin binds the RORα/RZR family. Studies of the peripheral distribution of melatonin receptors are important since they are attractive targets for immunomodulation, regulation of endocrine, …
Cytomegalovirus Cc Chemokine Promotes Immune Cell Migration,
2012
Chapman University
Cytomegalovirus Cc Chemokine Promotes Immune Cell Migration, Jennifer Totonchy, Michael Denton, Craig N. Kreklywich, Takeshi Andoh, Jessica M. Osborn, Daniel Chen, Ilhem Messaoudi, Susan L. Orloff, Daniel N. Streblow
Pharmacy Faculty Articles and Research
Cytomegaloviruses manipulate the host chemokine/receptor axis by altering cellular chemokine expression and by encoding multiple chemokines and chemokine receptors. Similar to human cytomegalovirus (HCMV), rat cytomegalovirus (RCMV) encodes multiple CC chemokine-analogous proteins, including r129 (HCMV UL128 homologue) and r131 (HCMV UL130 and MCMV m129/130 homologues). Although these proteins play a role in CMV entry, their function as chemotactic cytokines remains unknown. In the current study, we examined the role of the RCMV chemokine r129 in promoting cellular migration and in accelerating transplant vascular sclerosis (TVS) in our rat heart transplant model. We determined that r129 protein is released into culture …
A Thousand Tiny Pieces: The Federal Circuit’S Fractured Myriad Ruling, Lessons To Be Learned, And The Way Forward,
2012
American University Washington College of Law, Washington D.C.
A Thousand Tiny Pieces: The Federal Circuit’S Fractured Myriad Ruling, Lessons To Be Learned, And The Way Forward, Jonathan R. K. Stroud
IP Theory
No abstract provided.
The Effect Of Natural Antioxidants On Conjugated Linoleic Acid Yield During The Photoisomerization Of Soy Oil Linoleic Acid,
2012
University of Arkansas, Fayetteville
The Effect Of Natural Antioxidants On Conjugated Linoleic Acid Yield During The Photoisomerization Of Soy Oil Linoleic Acid, Camille Schaffner, Andy Proctor
Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences
Dietary conjugated linoleic acid (CLA) is known to be effective in avoiding many obesity related diseases. Conjugated linoleic acid is a product of ruminant fermentation and 3.4 g/day are needed to obtain the clinical benefits. However, it is difficult to obtain sufficient CLA to realize these benefits from a healthy diet containing dairy and beef products, without increasing levels of dietary cholesterol and saturated fat. A 20% CLA soy oil with low saturated fat and no cholesterol has been produced by photoisomerization of linoleic acid in the triacylglyceride oil. Further increasing the CLA yields has been possible by addition of …
Protein Structure Networks,
2012
Old Dominion University
Protein Structure Networks, Lesley H. Greene
Chemistry & Biochemistry Faculty Publications
The application of the field of network science to the scientific disciplines of structural biology and biochemistry, have yielded important new insights into the nature and determinants of protein structures, function, dynamics and the folding process. Advancements in further understanding protein relationships through network science have also reshaped the way we view the connectivity of proteins in the protein universe. The canonical hierarchical classification can now be visualized for example, as a protein fold continuum. This review will survey several key advances in the expanding area of research being conducted to study protein structures and folding using network approaches.
Kshv Infection Of Endothelial Cells Manipulates Cxcr7-Mediated Signaling: Implications For Kaposi’S Sarcoma Progression And Intervention,
2012
Chapman University
Kshv Infection Of Endothelial Cells Manipulates Cxcr7-Mediated Signaling: Implications For Kaposi’S Sarcoma Progression And Intervention, Jennifer Totonchy, Lisa Clepper, Janet Douglas, Liron Pantanowitz, Klaus Fruh, Ashlee V. Moses
Pharmacy Faculty Articles and Research
"CXCR7 was recently characterized as an alternative receptor for the chemokine CXCL12/SDF-1, previously thought to bind and signal exclusively through CXCR4.We recently identified CXCR7 as a key cellular factor in the endothelial cell (EC) dysfunction associated with KSHV infection. CXCL12 signaling is critically associated with tumor growth, angiogenesis and metastasis in several diverse tumors and is one of the most studied chemokine/chemokine receptor interactions in cancer systems. The tumorigenic activity of the CXCL12 signaling axis offers an attractive target for therapeutic intervention in multiple cancers including Kaposi’s Sarcoma (KS). However, most of the research to date was based on the …
A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells,
2012
Scripps College
A Proposal To Test The Effects Of Factor Ecat1 On Pluripotency, From Reprogramming To Differentiation Of Human Somatic Cells, Vritti R. Goel
CMC Senior Theses
The field of stem cell research has been growing more because of the interest in using stem cells to cure diseases and heal injuries. Human embryonic stem cells, because of the controversy surrounding them—and subsequently the difficulties in acquiring samples of the existing aging cell lines—can only be used in limited capacities. While the development of induced pluripotent stem cells in the last decade has allowed the field to progress closer to medical treatments, the low efficiency of reprogramming a somatic cell to a pluripotent state, and the vast molecular and genomic differences between human embryonic stem cells and human …
Simulating Molecular Mechanisms Of The Mdm2-Mediated Regulatory Interactions: A Conformational Selection Model Of The Mdm2 Lid Dynamics,
2012
Chapman University
Simulating Molecular Mechanisms Of The Mdm2-Mediated Regulatory Interactions: A Conformational Selection Model Of The Mdm2 Lid Dynamics, Gennady M. Verkhivker
Mathematics, Physics, and Computer Science Faculty Articles and Research
Diversity and complexity of MDM2 mechanisms govern its principal function as the cellular antagonist of the p53 tumor suppressor. Structural and biophysical studies have demonstrated that MDM2 binding could be regulated by the dynamics of a pseudo-substrate lid motif. However, these experiments and subsequent computational studies have produced conflicting mechanistic models of MDM2 function and dynamics. We propose a unifying conformational selection model that can reconcile experimental findings and reveal a fundamental role of the lid as a dynamic regulator of MDM2-mediated binding. In this work, structure, dynamics and energetics of apo-MDM2 are studied as a function of posttranslational modifications …
Effective Non-Viral Delivery Of Sirna To Acute Myeloid Leukemia Cells With Lipid-Substituted Polyethylenimines,
2012
University of Alberta
Effective Non-Viral Delivery Of Sirna To Acute Myeloid Leukemia Cells With Lipid-Substituted Polyethylenimines, Breanne Landry
Pharmacy Faculty Articles and Research
Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ~0.5 and led to siRNA/polymer complexes of …
