Biochemistry Commons^™

Inclusion Of Enclosed Hydration Effects In The Binding Free Energy Estimation Of Dopamine D3 Receptor Complexes, Rajat Kumar Pal, Satishkumar Gadhiya, Steven Ramsey, Pierpaolo Cordone, Lauren Wickstrom, Wayne W. Harding, Tom Kurtzman, Emilio Gallicchio

Publications and Research

Confined hydration and conformational flexibility are some of the challenges encountered for the rational design of selective antagonists of G-protein coupled receptors.We present a set of C3-substituted (-) -stepholidine derivatives as potent binders of the dopamine D3 receptor.The compounds are characterized biochemically, as well as by computer modeling using a novel molecular dynamics-based alchemical binding free energy approach which incorporates the effect of the displacement of enclosed water molecules from the binding site.The free energy of displacement of specific hydration sites is obtained using the Hydration Site Analysis method with explicit solvation. This work underscores the critical role of confined …

Bright Green Biofluorescence In Sharks Derives From Bromo-Kynurenine Metabolism, Hyun Bong Park, Yick Chong Lam, Jean P. Gaffney, James C. Weaver, Sara Rose Krivoshik, Randy Hamchand, Vincent Pieribone, David F. Gruber, Jason M. Crawford

Publications and Research

Although in recent years there has been an increased awareness of the widespread nature of biofluorescence in the marine environment, the diversity of the molecules responsible for this luminescent phenotype has been mostly limited to green fluorescent proteins (GFPs), GFP-like proteins, and fluorescent fatty acid-binding proteins (FABPs). In the present study, we describe a previously undescribed group of brominated tryptophan-kynurenine small molecule metabolites responsible for the green biofluorescence in two species of sharks and provide their structural, antimicrobial, and spectral characterization. Multi-scale fluorescence microscopy studies guided the discovery of metabolites that were differentially produced in fluorescent versus non-fluorescent skin, as …

The Fitness Landscape Of The African Salmonella Typhimurium St313 Strain D23580 Reveals Unique Properties Of The Pbt1 Plasmid, Rocío Canals, Roy R. Chaudhuri, Rebecca E. Steiner, Siân V. Owen, Natalia Quinones-Olvera, Melita A. Gordon, Michael Baym, Michael Ibba, Jay C. D. Hinton

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We have used a transposon insertion sequencing (TIS) approach to establish the fitness landscape of the African Salmonella enterica serovar Typhimurium ST313 strain D23580, to complement our previous comparative genomic and functional transcriptomic studies. We used a genome-wide transposon library with insertions every 10 nucleotides to identify genes required for survival and growth in vitro and during infection of murine macrophages. The analysis revealed genomic regions important for fitness under two in vitro growth conditions. Overall, 724 coding genes were required for optimal growth in LB medium, and 851 coding genes were required for growth in SPI-2-inducing minimal medium. These …

Case 64: Alkalosis In A Patient With A Brain Tumor: A Link Between The Cns And Blood Ph, Dr. Kathleen Cornely

Chemistry & Biochemistry Case Studies

The response of the carbonic acid/bicarbonate buffering system to a patient’s hyperventilation–presumably caused by CNS abnormalities following surgery to remove a brain tumor–is examined.

Creating A Molecular Map Of The Pediatric Lung, Quinlen F. Marshall

Forum Lectures

The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types that exhibit remarkable heterogeneity. (Whitsett, JA. et al. Physiol. Rev, 2019). Surprisingly, few studies have solely focused on human lung development during this critical period, and many current studies of lung maturation rely on adult, murine, or diseased samples, limiting their insights and applicability to longitudinal pediatric lung development. Understanding the molecular and physiological nuances of pulmonary development has important clinical relevance, …

The Alfalfa Insecticide Management (Aim) Toolkit: Linking Insecticide Fate Modelling With Alfalfa Pest And Beneficial Insect Toxicity Endpoints, Kimberly J. Hageman

Funded Research Records

No abstract provided.

Theoretical Studies Of Ir And Nmr Spectral Changes Induced By Sigma-Hole Hydrogen, Halogen, Chalcogen, Pnicogen, And Tetrel Bonds In A Model Protein Environment, Mariusz Michalczyk, Wiktor Zierkiewicz, Rafał Wysokiński, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Various types of σ-hole bond complexes were formed with FX, HFY, H₂FZ, and H₃FT (X = Cl, Br, I; Y = S, Se, Te; Z = P, As, Sb; T = Si, Ge, Sn) as Lewis acid. In order to examine their interactions with a protein, N-methylacetamide (NMA), a model of the peptide linkage was used as the base. These noncovalent bonds were compared by computational means with H-bonds formed by NMA with XH molecules (X = F, Cl, Br, I). In all cases, the A–F bond, which lies opposite the base and is responsible for …

Cold Atmospheric Plasma Induces Accumulation Of Lysosomes And Caspase-Independent Cell Death In U373mg Glioblastoma Multiforme Cells, Gillian Conway, Zhonglei He, Ana L. Hutanu, George P. Cribaro, Eline Manaloto, Alan Casey, Damien Traynor, Vladimir Milosavljevic, Orla Howe, Carlos Barcia, James T. Murray, Patrick J. Cullen, James Curtin

Articles

Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma …

Rompi-Cdsa: Ring-Opening Metathesis Polymerization-Induced Crystallization-Driven Self-Assembly Of Metallo-Block Copolymers, Ye Sha, Md Anisur Rahman, Tianyu Zhu, Yujin Cha, C Wayne Mcalister, Chuanbing Tang

Faculty Publications

Polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are among the most prevailing methods for block copolymer self-assembly. Taking the merits of scalability of PISA and dimension control of CDSA, we report one-pot synchronous PISA and CDSA ring-opening metathesis polymerization (ROMP) to prepare nano-objects based on a crystalline poly(ruthenocene) motif. We denote this self-assembly methodology as ROMPI-CDSA to enable a simple, yet robust approach for the preparation of functional nanomaterials.

Chemical Epitope Targeting: Review Of A Novel Screening Technology, Qurrat Ul-Ain, Rene Kandler, Dylan Gillespie, Arundhati Nag

Scholarly Undergraduate Research Journal at Clark (SURJ)

Chemical Epitope Targeting is a novel technology developed for designing peptide ligands with high affinity and specificity against specific regions of a protein that may be inaccessible to small molecules or antibodies. In this review, we summarize the key steps and significant applications of this technology. Operating on the same principles as antibody-antigen interactions, this technique involves chemically synthesizing the region of interest on the protein, called the epitope, as a polypeptide with a biotin detection tag and a strategically placed alkyne or azide presenting amino acid. The constructed epitope is screened against a comprehensive linear or cyclic One Bead …

Multigene Signatures Of Responses To Chemotherapy Derived By Biochemically-Inspired Machine Learning., Peter K. Rogan

Biochemistry Publications

Pharmacogenomic responses to chemotherapy drugs can be modeled by supervised machine learning of expression and copy number of relevant gene combinations. Such biochemical evidence can form the basis of derived gene signatures using cell line data, which can subsequently be examined in patients that have been treated with the same drugs. These gene signatures typically contain elements of multiple biochemical pathways which together comprise multiple origins of drug resistance or sensitivity. The signatures can capture variation in these responses to the same drug among different patients.

Minimalistic Peptide-Based Supramolecular Systems Relevant To The Chemical Origin Of Life, Daniela Kroiss

Dissertations, Theses, and Capstone Projects

All forms of life are based on biopolymers, which are made up of a selection of simple building blocks, such as amino acids, nucleotides, fatty acids and sugars. Their individual properties govern their interactions, giving rise to complex supramolecular structures with highly specialized functionality, including ligand recognition, catalysis and compartmentalization. In this thesis, we aim to answer the question whether short peptides could have acted as precursors of modern proteins during prebiotic evolution. Using a combination of experimental and computational techniques, we screened a large molecular search space for peptide sequences that are capable of forming supramolecular complexes with adenosine …

Exploration Of The Inhibitory Properties Of The Nucleoside Antibiotic Salicyl-Ams And Analogues Targeting Siderophore Biosynthesis In Mycobacterium Tuberculosis, Glennon Bythrow

Dissertations, Theses, and Capstone Projects

Mycobacterium tuberculosis (Mtb) is a resilient, obligate bacterial pathogen responsible for pulmonary tuberculosis disease (TB), that has upheld a significant impact on global public health throughout history. The World Health Organization (WHO) approximates nearly 10 million new TB cases arose in 2017 alone, accounting for 1.6 million deaths. There has been a notable rise in TB cases produced by multidrug‑resistant (MDR) and extensively drug-resistant (XDR) strains of Mtb. This, along with the intrinsic resistance of Mtb to many standard drugs and poor patient compliance, is deeply impacting global control of TB. Among the several strategies currently in …

Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly

Dissertations, Theses, and Capstone Projects

The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in …

Innate Antibodies, Murine Models, And Evolution: A Study Of Trypanosome Lytic Factor Functions And Their Translational Applications, Joseph P. Verdi

Dissertations, Theses, and Capstone Projects

Trypanosome lytic factors (TLFs) are primate-specific antimicrobial protein complexes that lyse African trypanosome parasites by delivering the channel-forming toxin APOL1 to the invading microorganisms. Human serum contains two TLFs that are delivered to the parasite by separate mechanisms, only one of which has been characterized. TLF1 is endocytosed by a receptor that is typically blocked by other serum factors in vivo, suggesting that TLF2 is the more relevant lytic factor in the context of trypanosome immunity. TLF2 is non-covalently associated with polyclonal immunoglobulin M (IgM) antibodies, which we report here to be involved in the uptake mechanism. The TLF2-IgMs …

Engineering Of Escherichia Coli 2-Oxoglutarate Dehydrogenase Complex With Mechanistic And Synthetic Goals, Joydeep Chakraborty

Dissertations

The Escherichia coli 2-oxoglutarate dehydrogenase complex (OGDHc) compromises multiple copies of three enzymes - 2-oxoglutarate dehydrogenase (E1o), dihydrolipoyl succinyltransferase (E2o), and dihydrolipoyl dehydrogenase (E3). OGDHc is found in the Krebs cycle and catalyzes the formation of the all-important succinyl-Coenzyme A (succinyl-CoA). OGDHc was engineered to understand the catalytic mechanism and optimized for chemical synthetic goals.

Succinyl-CoA formation takes place within the catalytic domain of E2o via a transesterification reaction. The succinyl group from the thiol ester of S8-succinyldihydrolipoyl-E2o is transferred to the thiol group of CoA. Mechanistic studies were designed to investigate enzymatic transthioesterification. His375 and Asp374 was shown to …

Anisotropic Singlet Fission In Single Crystalline Hexacene, Dezheng Sun, Gang-Hua Deng, Bolei Xu, Enshi Xu, Xia Li, Yajing Wu, Yuqin Qian, Yu Zhong, Colin Nuckolls, Avetik R. Harutyunyan, Hai-Lung Dai, Gugang Chen, Hanning Chen, Yi Rao

Chemistry and Biochemistry Faculty Publications

Singlet fission is known to improve solar energy utilization by circumventing the Shockley-Queisser limit. The two essential steps of singlet fission are the formation of a correlated triplet pair and its subsequent quantum decoherence. However, the mechanisms of the triplet pair formation and decoherence still remain elusive. Here we examined both essential steps in single crystalline hexacene and discovered remarkable anisotropy of the overall singlet fission rate along different crystal axes. Since the triplet pair formation emerges on the same timescale along both crystal axes, the quantum decoherence is likely responsible for the directional anisotropy. The distinct quantum decoherence rates …

Spectroscopic Description Of The E1 State Of Mo Nitrogenase Based On Mo And Fe X‑Ray Absorption And MöSsbauer Studies, Casey Van Stappen, Roman Davydov, Zhi-Yong Yang, Ruixi Fan, Yisong Guo, Eckhard Bill, Lance C. Seefeldt, Brian M. Hoffman, Serena Debeer

Chemistry and Biochemistry Faculty Publications

Mo nitrogenase (N2ase) utilizes a two-component protein system, the catalytic MoFe and its electron-transfer partner FeP, to reduce atmospheric dinitrogen (N₂) to ammonia (NH₃). The FeMo cofactor contained in the MoFe protein serves as the catalytic center for this reaction and has long inspired model chemistry oriented toward activating N₂. This field of chemistry has relied heavily on the detailed characterization of how Mo N2ase accomplishes this feat. Understanding the reaction mechanism of Mo N2ase itself has presented one of the most challenging problems in bioinorganic chemistry because of the ephemeral nature of its …

An Exploration Of Protein And Dna Components In Fingerprint Residue, Ashley Borrego

Student Theses

The main focus of this project was to investigate the protein and DNA components in both sebaceous and eccrine fingerprints. This study investigated the relative content of DNA and proteins in eccrine fingerprints to sebaceous fingerprints. All volunteers were instructed to wash and dry their hands prior to depositing parallel thumbprints. Twenty volunteers were instructed to touch their face to produce sebaceous prints, and 5 volunteers were instructed to wear gloves over a heat source to produce sweaty or eccrine prints. Microscopy was used to score the cellular debris of the right fingerprint on a scale of 1-4 based on …

Trophic Upgrading And Mobilization Of Wax Esters In Microzooplankton, Keyana Roohani, Brad A. Haubrich, Kai-Lou Yue, Nigel D'Souza, Amanda Mantalbano, Tatiana Rynearson, Susanne Menden-Deuer, Christopher Reid

Science and Technology Department Faculty Journal Articles

Heterotrophic protists play pivotal roles in aquatic ecosystems by transferring matter and energy, including lipids, from primary producers to higher trophic predators. Using Oxyrrhis marina as a model organism, changes to the non-saponifiable protist lipids were investigated under satiation and starvation conditions. During active feeding on the alga Cryptomonas sp., the O. marina hexane soluble non-saponifiable fraction lipid profile reflected its food source with the observed presence of long chain mono-unsaturated fatty alcohols up to C25:1. Evidence of trophic upgrading in O. marina was observed with long chain mono-unsaturated fatty alcohol accumulation of up to C35:1. To the best of …

Understanding Excitation Energy Quenching In Isia, Hui-Yuan Steven Chen

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cyanobacteria are photoautotrophic organisms that contribute a significant amount of global primary productivity. They are found in freshwater, marine and even some extremely severe environments. Among those environments, iron deficiency is one of the most common stress conditions in cyanobacterial habitats. To survive, cyanobacteria have evolved and developed several strategies to alleviate the damage caused by iron deficiency.

Iron stress-inducible protein (IsiA) is a chlorophyll-binding membrane protein found in cyanobacteria grown in iron-deficient conditions. During the past decades, considerable effort has been put on understanding how IsiA functions to help cyanobacteria survive iron deficiency. It has been reported that IsiA …

Selective Alteration Of The Root Morphology Of Arabidopsis Thaliana By Synthetic Anion Transporters (Sats), Mohit Patel, Evan Garrad, Steven Korb, Saeedeh Negin, Michael Gokel, Sergey Sedinkin, Shanheng Yin, George Gokel

Chemistry & Biochemistry Faculty Works

No abstract provided.

Synthesis And Evaluations Of “1,4-Triazolyl Combretacoumarins” And Desmethoxy Analogs, Tashrique A. Khandaker, Jessica D. Hess, Renato Aguilera, Graciela Andrei, Robert Snoeck, Dominique Schols, Padmanava Pradhan, Mahesh K. Lakshman

Publications and Research

1,4-Triazolyl combretacoumarins have been prepared by linking the trimethoxyarene unit of combretastatin A4 with coumarins, via a 1,2,3-triazole. For this, 4-azidocoumarins were accessed by a sequential two-step, one-pot reaction of 4-hydroxycoumarins with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), followed by reaction with NaN₃. In the reaction with BOP, a coumarin-derived phosphonium ion intermediate seems to form, leading to an O⁴-(benzotriazolyl)coumarin derivative. For the CuAAC reaction of azidocoumarins with 5-ethynyl-1,2,3-trimethoxybenzene, catalytic [(MeCN)₄Cu]PF₆ in CH₂Cl₂/MeOH with 2,6-lutidine, at 50 ^oC, was suitable. The 4-azidocoumarins were less reactive as compared to PhN₃ and …

Characterization Of Endothelial Nitric Oxide Synthase Serine-600 Phosphorylation, Kevin Patel

Master of Science in Chemical Sciences Theses

Endothelial nitric oxide synthase (eNOS) is part of a family of three nitric oxide synthase (NOS) enzymes that catalyze the production of nitric oxide (NO). NO is a gaseous, free-radical signaling molecule that has a variety of cellular and physiological functions that range from maintaining cardiovascular homeostasis to neurotransmission. The function of NO greatly depends on the concentration and is cell type specific. eNOS is the most regulated of the three NOS isoforms and the mechanisms of regulation can be through protein-protein interactions and posttranslational modifications. A connection with eNOS and the cell cycle has begun to form with recent …

Investigation Of The Electrode Polarization Effect For Biosensor Applications, Anil Koklu

Mechanical Engineering Research Theses and Dissertations

My research focuses on electrokinetic transport. Particularly, in this dissertation, we focus on fabrication and testing of micro electrodes with nanostructured surfaces to minimize the electrode polarization (EP) effects for biosensor applications. In the first study, electrochemical deposition of gold nanoparticles on to planar gold electrodes was used to generate rough surfaces. Dendritic nanostructures that reduced EP up to two orders of magnitude was obtained by optimizing the deposition conditions. These structures also enhanced dielectrophoresis (DEP) response of our bio-chips, making them usable in physiological buffers. In further studies we discovered a universal scaling of EP in the frequency domain, …

Parallel Multipole Expansion Algorithms And Their Biology Applications, Jiahui Chen

Mathematics Theses and Dissertations

N-body pairwise interactions are ubiquitous in scientific areas such as astrophysics, fluids mechanics, electrical engineering, molecular biology, etc. Computing these interactions using direct sum of an O(N) cost is expensive, whereas multipole expansion methods, such as the fast multipole method (FMM) or treecode, can reduce the cost to O(N) or O(N log N). This thesis focuses on developing numerical algorithms of Cartesian FMM and treecode, as well as using these algorithms to directly or implicitly solve biological problems involving pairwise interactions. This thesis consists of the following topics. 1) A cyclic parallel scheme is developed to handle the load balancing …

How To Untie A Protein Knot., Sitao Yin, Brittiny Dhital, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

The origin of protein backbone threading through a topological knot remains elusive. To understand the evolutionary origin of protein knots, in this issue of StructureKo et al. (2019) used circular permutation to untie a knotted protein. They showed that a domain-swapped dimer releases the knot and the associated high-energy state for substrate binding.

Iron-Sulfur Cluster Assembly; In Vivo Analysis Of The Methanogenic Suf System, Evan Dunkle

LSU Master's Theses

Iron-sulfur (Fe-S) clusters are among the most ancient and prevalent of all biological cofactors. Their assembly into associated proteins is a tightly regulated process with many organisms employing multiple cluster assembly pathways. Much is known about Fe-S cluster assembly in aerobic organisms such as Escherichia coli (E. coli) but little is known in regards to cluster assembly in more ancient organisms such as methanogens. Methanogens are members of the domain of Archaea and are defined by their ability to generate methane as a byproduct of their main energy generating pathway. Methanogens also have significantly higher Fe-S cluster content …

Podophyllum Peltatum: Relationship Of Colony Size And Age, Emily Holst, Heidi Keswick, David P. Warners

Student Papers and Reports

No abstract provided.

Stormwater Capture Via Green Infrastructure In The Plaster Creek Watershed, Kyle Dankert, Ana Singh, Deanna Geelhoed, David P. Warners

Student Papers and Reports

No abstract provided.