bluuebunny/crossref_metadata_2025_split huggingface dataset:
LargeG‐Proteins
Authors: Siderovski David P. , Kimple Adam J. , Willard Francis S. 
Published: February 2008

AbstractLarge G‐proteins, also known as heterotrimeric G‐proteins, cycle through inactive (GDP‐bound) and active (GTP‐bound) states, thereby coupling the activation of cell‐surface receptors to the modulation of various second messengers and intracellular effector proteins. High‐resolution structures of the constituent subunits of the heterotrimer (Gα, Gβ, and Gγ) have revealed the determinants involved in heterotrimer assembly and effector protein engagement as well as the mechanism of nucleotide hydrolysis by the Gα subunit and its acceleration by “regulator of G‐protein signaling” (RGS) proteins. Mechanistic details have also been gleaned from studies of G‐protein modulation by pathogen toxins and chemicals such as aluminum tetrafluoride. Recent identification of peptide‐binding “hotspots” on G‐protein subunits should facilitate discovery and design of new chemical entities that can modulate nucleotide cycling and receptor/effector coupling at the level of the G‐protein heterotrimer.
Inositol Polyphosphates
Authors: Resnick Adam C. , Saiardi Adolfo 
Published: February 2008

AbstractInositol polyphosphates comprise a large family of water‐soluble molecules derived from the combinatorial phophorylation of the six hydroxyls ofmyo‐inositol. Second messenger roles for inositol polyphosphates in Ca2+mobilization were first identified for what is now the best characterized family member, inositol 1,4,5‐trisphosphate (InsP3). Additional anabolic and catabolic metabolism of InsP3results in the formation of a large, diverse family of higher inositol polyphosphates whose signaling roles and biologic functionality remain largely undefined. However, the recent cloning and identification of the kinases and phosphatases involved in the combinatorial modification of inositol polyphosphates has served to further define and characterize this complex metabolic network and to identify its preeminence in nearly all aspects of cell biology. Conserved from yeast to humans, inositol polyphosphates regulate a wide array of processes, including ion‐channel conductance, membrane dynamics, transcription, nucleic acid metabolism, and protein phosphorylation.
Lipid Domains, Chemistry of
Authors: Epand Richard M. 
Published: February 2008

Abstract
Biological membranes are composed largely of proteins and lipids. A wide range of molecular structures exists among these molecules. It is therefore not surprising that biological membranes are not uniform but rather cluster certain molecules in specific regions or domains. This behavior can be mimicked in model systems comprising a limited number of components to study in more detail the molecular nature of this domain formation. Two types of domains exist that have been more extensively studied. One is a membrane domain enriched in polyanionic lipids, such as phosphatidylinositol diphosphate. Such domains are formed by the presence of proteins with segments containing several cationic amino acid residues. Such proteins have been termed “pipmodulins.” Another kind of domain is formed as a consequence of the nonuniform distribution of cholesterol in the membrane. Caveolae represent one type of cholesterol‐rich domain that is well characterized. Other cholesterol‐rich domains are termed “rafts.” Characterization of rafts in model membranes is well documented, but the nature of cholesterol‐rich domains in biological membranes remains a subject of controversy. Several imaging and fluorescence methods are being employed to further characterize the size and lifetime of small raft domains in biological membranes.
Lipid Homeostasis, Chemistry of
Authors: Black Paul N. , Sealls Whitney , DiRusso Concetta C. 
Published: February 2008

AbstractLipid metabolism encompasses a large part of intermediary metabolism and includes highly dynamic processes, which are subject to regulation at transcriptional and enzymatic levels. The maintenance of lipid metabolism or lipid homeostasis is multilayered and includes biosynthesis and degradation, the impact of external stimuli proceeding through signal transduction, the function of lipid‐responsive transcription factors, and lipid trafficking. It also includes the production of bioactive lipids, which have regulatory roles in different lipid metabolic pathways, effect specific transcription factors, and influence a myriad of cellular processes. Lipid metabolism is responsive to external supplies of fatty acids and other precursors required for neutral lipid, glycerol phospholipid, and sphingolipids synthesis. In some cell types, fatty acid composition within membrane lipids must necessarily adapt to changes in temperature to maintain appropriate fluidity essential for biologic activity. Finally, lipids are diverse in both structure and abundance and differ among animals, plants, fungi, and bacteria. This article will focus on the fatty acid metabolism and, to some extent, its relationship to sterol metabolism, which underpins lipid homeostasis. Readers are referred to other articles in this series (see cross‐references below), particularly on steroid and lipid synthesis, chemistry and chemical reactivity of lipids, and lipidomics.
Lipids: Phase Transitions
Authors: Koynova Rumiana , Tenchov Boris 
Published: February 2008

AbstractLipids constitute a diverse group of biomolecules of varied biologic roles. Their major function is to serve as building blocks of the biologic membranes. According to the fluid‐mosaic model, the biomembranes are liquid‐crystalline lipid bilayers with embedded proteins. This model includes two references to the lipid phase state—liquid crystallineandbilayer—both of which are of critical importance for the proper membrane functioning. The majority of lipids are amphiphilic compounds, which, similarly to other surfactants, also can form a large variety of other, non‐liquid‐crystalline and nonbilayer phases by transforming into each other via different kinds of phase transitions. In particular, the impressive variety of lipids in the biomembranes includes a large fraction of species that in isolation prefer to adopt curved, hexagonal, or cubic phases rather than the lamellar phase. The physiologic importance of the lipid diversity and mesomorphic behavior stems from the possibility of finely tuning and optimizing the properties of the biomembranes by regulating their lipid composition.
Lipidomics
Authors: Farwanah Hany , Kolter Thomas 
Published: February 2008

Abstract
Lipids are hydrophobic or amphiphilic low‐molecular‐weight substances with a low solubility in water. Glycerophospholipids, sphingolipids, and cholesterol are the building blocks of cellular membranes, and triacylglycerols are the major molecular storage forms of metabolic energy. Various lipids serve as signaling substances either as first or second messengers in signal transduction; as autocrinic, paracrinic, or endocrinic regulators; or are covalently bound to cellular proteins. Several diseases are caused by, or at least associated with, alterations in lipid metabolism, such as inherited disorders of lipid metabolism, atherosclerosis, diabetes, obesity, or Alzheimer's disease.
Lipids: Chemical Diversity
Authors: Guschina Irina A. , Harwood John L. 
Published: February 2008

Abstract
Lipids represent some of the most complex biologic molecules, and their diversity is crucial for their cellular functions. The wide range of chemical and physical properties of different lipids determines a variety of roles for these compounds in biologic processes. According to their structures, lipids can be divided into two main groups: the nonpolar lipids (acylglycerols, sterols, free fatty acids, hydrocarbons, alcohols, wax, and steryl esters) and the polar lipids (phosphoglycerides, glycosylglycerides, and sphingolipids). Triacylglycerols act as energy stores and metabolic fuels. Polar lipids and sterols are important structural components of cell membranes where they may have many diverse functions. Arranged as bilayers, they establish permeability barriers for cells and organelles and provide a microenvironment for membrane‐associated proteins as well as participate directly in metabolism and a multitude of membrane fusion events (1). Waxes as surface coverings are integral to water balance and protect organisms from noxious environmental conditions. In addition to a structural role, lipids serve as important intermediates in cell signaling pathways (e.g., sphingolipids, inositol lipids, phosphatidic acid, lysophospholipids, oxidative products) and play a role in mediating cellular responses to the environment (2). In this article, we will summarize our knowledge on the structural diversity of lipids that provide information on the various lipid classes and the fatty acids that occur naturally.
Metal Homeostasis
Authors: Outten F. Wayne , Twining Benjamin S. 
Published: February 2008

AbstractTransition metals are a key component of biological systems. Because of their special properties, they are incorporated into proteins functioning in dioxygen transport, electron transfer, redox transformations, and regulatory control. The metals used in biological systems have been selected throughout evolution based on their availability in the environment and their kinetic lability, resulting in preferential use of first‐row transition metals in biology. These essential metals must be obtained from the environment and concentrated within the cell for use in biochemical pathways. Once appropriated, metals must be directed to metalloenzymes or metal storage proteins within the cell. In addition, organisms must be able to distinguish between essential and toxic metals and must have mechanisms for minimizing the toxicity of both essential and toxic metals that are present in excess. Metal homeostasis is broadly defined as the metal uptake, trafficking, efflux, and sensing pathways that allow organisms to maintain an appropriate (often narrow) intracellular concentration range of essential transition metals. This review will introduce several unifying concepts of metal homeostasis with brief illustrative examples for each concept.
Metallo‐Enzymes and Metallo‐Proteins, Chemistry of
Authors: Williams Robert J.P. 
Published: February 2008

AbstractMetallo‐enzymes and metallo‐proteins are a combination of a metal ion or several metal ions in which the metal ion is strongly held in a protein. Hence, before describing their properties and functions, it is necessary to appreciate which metal ions bind strongly to proteins and exchange slowly. The biological significance of metallo‐enzymes is that they are essential catalysts, especially for the metabolism of small molecules such as H2, CH4, CO, N2, and O2, as well as for long‐range electron transfer. The control of uptake and the synthesis of their proteins rest with feedback in a series of metallo‐proteins.
Metallointercalators as Probes of DNA Recognition and Reactions
Authors: Augustyn Katherine E. , Pierre Valerie C. , K. Barton Jacqueline 
Published: February 2008

Abstract
Here we describe studies of metallointercalators bound to DNA. These octahedral transition metal complexes primarily bind noncovalently by stacking within the DNA helix. Given the rich photophysics and photochemistry of the ruthenium and rhodium complexes we employ, we have used a variety of biophysical studies to characterize their interactions with DNA. X‐ray crystallography has also provided atomic resolution detail as to their binding to the duplex. Complexes have been designed that target DNA with high specificity. We have, for example, designed metal complexes that bind specifically to mismatched sites in the DNA duplex, and these have found application in the detection of single nucleotide polymorphisms and studies of mismatch repair deficiency. The photophysical properties of the metal complexes along with their intercalative stacking have been useful in particular as tools to characterize long‐range charge transport in DNA. Using metallointercalators tethered to the duplex, oxidative damage to DNA from a distance has been demonstrated. The metallointercalators may serve as models for DNA‐binding proteins, not only in binding DNA sites with high specificity, but also in carrying out electron transfer chemistry mediated by the DNA base‐pair stack. Certainly these metallointercalators have proven to be powerful probes of this chemistry.
Metalloregulatory Proteins
Authors: Zamble Deborah B. 
Published: February 2008

AbstractMetalloregulators are proteins that bind metals and modulate gene expression through direct interactions with DNA or RNA. The genes under this metal‐dependent control encode a variety of proteins involved in the cellular homeostasis of both essential and toxic metals. Metalloregulators are present in all types of organisms, and extensive information exists about their mechanisms, although many unanswered questions remain. The global activities of these metal‐responsive factors require overcoming complex challenges, such as the manner in which the proteins regulate gene expression, the mechanisms of the metal‐dependent protein conformation transformations, and the ability of the proteins to recognize the designated metal(s). An understanding of these key biomolecules draws from disciplines such as cell biology, protein chemistry, and inorganic chemistry and provides molecular insight into one fundamental aspect of life.
Metals in Medicine: Imaging Agents
Authors: Caravan Peter 
Published: February 2008

AbstractThe use of metal ions in diagnostic medicine is widespread. Metal complexes and nanoparticles are used clinically in magnetic resonance imaging, nuclear medicine (gamma scintigraphy and positron emission tomography), and X‐ray imaging. Preclinically, additional advances are being made in these fields through the creative application of metal complexes and metal‐containing nanoparticles. This article briefly describes different clinical imaging modalities and the physico‐chemical properties required for imaging agents. Commercial agents are used to illustrate these properties and to describe the clinical state of the art. Selected examples of exciting preclinical imaging agents that have shown efficacyin vivoalso are described.
AdoMet‐Dependent Methyltransferases, Chemistry of
Authors: Klimasauskas Saulius , Lukinavicius Grazvydas 
Published: February 2008

AbstractS‐adenosyl‐L‐methionine is a high energy compound and is the major source of methyl groups for a myriad of biologic transmethylation reactions. These highly specific single‐carbon transfers onto diverse nucleophilic centers in biomolecules are catalyzed by methyltransferase enzymes and play important regulatory and structural roles in the cell. Here we discuss the chemical mechanism of the methylation reactions, including structural features of the methylsulfonium center in the cofactor molecule, enzyme‐assisted activation of diverse nucleophilic targets by deprotonation or covalent catalysis, and spatial constraints of the reaction.
Mitochondrial Medicine
Authors: Rodenburg Richard J.T. , Smeitink Jan A.M. 
Published: February 2008

Abstract
Mitochondrial medicine is an emerging field in medicine that focuses on diseases in which the mitochondrial energy generating system plays a central role. These diseases include the “classical” mitochondrial disorders, in which a (genetic) defect in the mitochondrial energy generating system is the primary cause of the disease, but also more common disorders such as Parkinson and cancer, in which mitochondrial energy metabolism plays an important role in the pathogenesis. In this review, we present an overview of the mitochondrial energy generating system, starting at the conversion of pyruvate into acetyl‐CoA by pyruvate dehydrogenase, via the TCA cycle in which reduction equivalents are formed, to the oxidative phosphorylation system, where the reduction equivalents are used to convert ADP into ATP. The mitochondrial energy generating system can be examined by global assays that measure the rate of pyruvate conversion, the rate of oxygen consumption, or the rate of ATP production. In addition, an overview is given of the spectrophotometric assays that are available to measure PDHc, several TCA cycle enzymes, and the enzymes of the oxidative phosphorylation. In the diagnostic analysis of patients suspected to suffer from a mitochondrial disorder, these assays are applied to evaluate the functioning of the mitochondrial energy generating system in muscle biopsies and other types of patient samples. In addition, the results provide clues for further investigations at the molecular genetic level. Thus, the biochemical analysis of patient material is an important step in establishing the diagnosis of a mitochondrial disorder.
Natural Products as Anticancer Agents
Authors: Kingston David G. I. , Newman David J. 
Published: February 2008

Abstract

Natural products have provided some of the most effective drugs for the treatment of cancer, including such well‐known drugs as paclitaxel (Taxol
™
; Bristol‐Myers Squibb) adriamycin, vinblastine, and vincristine. Natural products have also provided many compounds that have led to the discovery of new biochemical mechanisms. This review summarizes the major natural products in clinical use today and introduces several new ones on the cusp of entering clinical practice. The review is organized by mechanism of action, with compounds that interact with proteins discussed first, followed by compounds that interact with RNA or DNA.
Nature: A Model System for Chemists
Authors: Breslow Ronald 
Published: February 2008

Abstract
Chemists have learned to imitate the principles of biologic chemistry in the quest to produce artificial enzymes, artificial receptors, and, ultimately, artificial living cells. The field of natural products chemistry is concerned chiefly with discovering the structures of the molecules produced in living systems as well as the paths by which they are produced. Biomimetic chemistry takes nature as a model and extends what exists in biology into what is possible. This process includes using hydrophobic effects in water to achieve selective reactions and making new amino acids and new nucleotides to generalize the properties of proteins and nucleic acids. Potent new catalysts are based on the chemistry performed by coenzymes using bifunctional acid–base catalysis and the water exclusion achieved by natural enzymes. Exciting new areas include molecular machines, mimics of the chemical senses, and work on the origin on earth of the homochirality observed in biomolecules. The studies using nature as a model have enriched chemistry greatly and furnished interesting insights into biochemistry.
NMR
: Lipids
Authors: Dufourc Erick J. 
Published: February 2008

Abstract
Lipid structure and dynamics are keys factors for cell life. Phospholipids are essential in signalling pathways as they are recognition sites at the membrane surface. Other lipids such as cholesterol and sphingomyelin are crucial molecules in maintaining membrane integrity and are involved in membrane domains (rafts). NMR both with its liquid and solid‐state facets is a very powerful tool for deciphering both the structure and the dynamics of various classes of lipids. Lipids extracted from membranes and dissolved in organic solvents can reveal their molecular structure when observed with multinuclear one‐dimensional or two‐dimensional solution NMR. Multinuclear, wide‐line, solid‐state NMR brings information on the nature of the membrane phase (lamellar, hexagonal, isotropic, etc.), its dynamics (diffusion, fluid/gel, or liquid‐ordered with cholesterol) and the molecular structure of embedded lipids when using the Magic Angle Spinning technique.
NMR: Proteins
Authors: Gronenborn Angela M. 
Published: February 2008

AbstractSolution NMR methods for determining three‐dimensional, atomic resolution structures and dynamic properties of biologic macromolecules are well established. Currently, an ever‐increasing number of experimentally solved protein NMR structures is available and contributes to our understanding of biology. The development of novel NMR approaches, labeling techniques, and calculational algorithms allows the study of larger and more complex systems. Here I summarize the basic NMR approaches, discuss labeling and assignment strategies, and provide examples for their uses.
Artificial Metalloproteins: Design and Engineering
Authors: Lu Yi , Garner Dewain K. , Zhang Jun‐long 
Published: February 2008

Abstract
Engineering of artificial metalloproteins is an expanding field with potential impacts in many areas from fundamental understanding of protein structure and function to industrial production of specialty chemicals such as chiral drug intermediates. Incorporation of unnatural amino acids and non‐native metal cofactors into proteins is an emerging field in the area of protein design, as it offers the tantalizing prospect of introducing new functionality and provides exquisite probes for and fine‐tuning of native protein properties. Although it is a relatively young field, engineering of non‐native metalloproteins boasts a myriad of techniques for design, construction, and/or expression of the desired artificial protein. Additionally, many groundbreaking studies exist in this field that have enhanced basic scientific understanding of protein function or generated promising artificial enzymes. Discussion of the techniques prominent for incorporation of unnatural amino acids and non‐native cofactors is followed by some of the most interesting applications of these techniques reported to date.
Nucleic Acids: Hydration
Authors: Chalikian Tigran V. , Völker Jens 
Published: February 2008

Abstract
Water is an integral part of DNA structure, and it plays an important role in dictating conformational preferences and binding properties of nucleic acids. Although in recent years a wealth of information on the physical properties of water in the vicinity of nucleic acids has accumulated, our understanding of how water interacts with nucleic acids and how it mediates DNA recognition by small ligands and DNA‐binding proteins remains limited. In this article, we review the current state of DNA hydration research. In particular, we discuss structural, dynamic, and thermodynamic aspects of nucleic acid hydration. We also present an overview of the structural and thermodynamic role of water in modulating protein–DNA recognition and highlight the importance of hydration as a major contributor to the energetics of nucleic acid recognition. We emphasize the need for additional physico‐chemical studies of DNA hydration by experimental and theoretic scientists.
Oxygen‐Activating Enzymes, Chemistry of
Authors: R. Hess Corinna , W. D. Welford Richard , P. Klinman Judith 
Published: February 2008

AbstractAerobic organisms derive the energy required for cellular processes from the conversion of dioxygen to water, which highlights the importance of dioxygen chemistry in biologic systems. The biochemistry of dioxygen is far from simple and has been the subject of intense study in a range of chemical and biologic disciplines. The reduction of dioxygen is energetically favorable; however, dioxygen is a ground state triplet, kinetically unreactive with singlet organic molecules. Nature has developed a diverse array of catalysts to overcome this kinetic barrier. These dioxygen‐activating enzymes are divided into two classes: oxygenases and oxidases. Oxygenases incorporate directly at least one atom from dioxygen into the organic products of their reaction. Oxidases couple the reduction of dioxygen with the oxidation of substrate. Typically, enzymes that react with dioxygen contain transition metal ions and/or conjugated organic molecules as cofactors. The reaction with dioxygen is initiated by electron transfer from the cofactor to O2. The subsequent chemistry varies depending on both the nature of the cofactor and the protein scaffold. Here we review the fascinating chemistry of the dioxygen‐activating enzymes and identify some of the common strategies and themes that have emerged from over half a century of research.