Inorganic Compounds Essential to Human Functioning

MINIREVIEW Mixed lineage leukemia: histone H3 lysine 4 methyltransferases from yeast to human Shivani Malik and Sukesh R. Bhaumik Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL, USA Introduction The DNA in eukaryotes is compacted in the form of chromatin. The fundamental unit of chromatin is the nucleosome which consists of a core histone particle with 146 bp of DNA wrapped around it [1,2]. The core histone particle comprises a tetramer of histones H3 and H4 and dimers of histones H2A and H2B [2]. Each of these histones has a structured core globular domain and an unstructured flexible N-terminal tail protruding from the core domain. The linker histone H1 associates with the core domain to form a higher order structure, thus further compacting the DNA [3,4]. Such compac- tion of DNA in a higher order chromatin structure makes it inaccessible for proteins involved in different DNA-transacting processes such as transcription, repli- cation, recombination and DNA repair. However, the chromatin structure has to be dynamic in nature in order for DNA-transacting processes to occur [5–10], and such dynamic states are regulated by ATP-depen- dent chromatin remodelers as well as by ATP-indepen- dent histone covalent modifications. There are several ATP-dependent chromatin remo- delers. These include the switching–defective ⁄ sucrose non-fermenting (SWI ⁄ SNF), imitation switch (ISW1), nucleosome remodeling and histone deacetylation (Mi-2 ⁄ NuRD), and INO80 complexes [11–25]. These complexes have a catalytic ATPase subunit with Keywords ASH1; ASH2; COMPASS; histone H3 lysine 4; histone methyltransferase; MLL; Set1; TAC1; TRX; WDR5 Correspondence S. R. Bhaumik, Department of Biochemistry and Molecular Biology, Southern Illinois University School of Medicine, Carbondale, IL 62901, USA Fax: +1 618 453 6440 Tel: +1 618 453 6479 E-mail: sbhaumik@siumed.edu (Received 16 November 2009, revised 12 January 2010, accepted 22 January 2010) doi:10.1111/j.1742-4658.2010.07607.x The fourth lysine of histone H3 is post-translationally modified by a methyl group via the action of histone methyltransferase, and such a covalent modification is associated with transcriptionally active and ⁄ or repressed chromatin states. Thus, histone H3 lysine 4 methylation has a crucial role in maintaining normal cellular functions. In fact, misregulation of this covalent modification has been implicated in various types of cancer and other diseases. Therefore, a large number of studies over recent years have been directed towards histone H3 lysine 4 methylation and the enzymes involved in this covalent modification in eukaryotes ranging from yeast to human. These studies revealed a set of histone H3 lysine 4 methyltransfe- rases with important cellular functions in different eukaryotes, as discussed here. Abbreviations ASH1, absent, small or homeotic discs 1; ASH2, absent, small or homeotic discs 2; BRM, brahma; CBP, CREB-binding protein; EcR, ecdysone receptor; HAT, histone acetyl transferase; H3K4, histone H3 lysine 4; HMT, histone methyltransferase; MLL, mixed lineage leukemia; MOF, male absent on the first; Paf1, RNA polymerase II-associated factor 1; PcG, polycomb group; PHD, plant homeodomain; TAC1, trithorax acetylation complex 1; TRR, trithorax-related; TRX, trithorax. FEBS Journal 277 (2010) 1805–1821 ª 2010 The Authors Journal compilation ª 2010 FEBS 1805 DNA-dependent ATPase activity. ATP-independent histone covalent modifications are acetylation, phos- phorylation, ubiquitylation, methylation, sumoylation and ADP ribosylation [8,10,26–33]. Although most of these modifications occur on the N-terminal tails Inorganic Compounds Essential to Human Functioning Inorganic Compounds Essential to Human Functioning Bởi: OpenStaxCollege The concepts you have learned so far in this chapter govern all forms of matter, and would work as a foundation for geology as well as biology This section of the chapter narrows the focus to the chemistry of human life; that is, the compounds important for the body’s structure and function In general, these compounds are either inorganic or organic • An inorganic compound is a substance that does not contain both carbon and hydrogen A great many inorganic compounds contain hydrogen atoms, such as water (H2O) and the hydrochloric acid (HCl) produced by your stomach In contrast, only a handful of inorganic compounds contain carbon atoms Carbon dioxide (CO2) is one of the few examples • An organic compound, then, is a substance that contains both carbon and hydrogen Organic compounds are synthesized via covalent bonds within living organisms, including the human body Recall that carbon and hydrogen are the second and third most abundant elements in your body You will soon discover how these two elements combine in the foods you eat, in the compounds that make up your body structure, and in the chemicals that fuel your functioning The following section examines the three groups of inorganic compounds essential to life: water, salts, acids, and bases Organic compounds are covered later in the chapter Water As much as 70 percent of an adult’s body weight is water This water is contained both within the cells and between the cells that make up tissues and organs Its several roles make water indispensable to human functioning 1/11 Inorganic Compounds Essential to Human Functioning Water as a Lubricant and Cushion Water is a major component of many of the body’s lubricating fluids Just as oil lubricates the hinge on a door, water in synovial fluid lubricates the actions of body joints, and water in pleural fluid helps the lungs expand and recoil with breathing Watery fluids help keep food flowing through the digestive tract, and ensure that the movement of adjacent abdominal organs is friction free Water also protects cells and organs from physical trauma, cushioning the brain within the skull, for example, and protecting the delicate nerve tissue of the eyes Water cushions a developing fetus in the mother’s womb as well Water as a Heat Sink A heat sink is a substance or object that absorbs and dissipates heat but does not experience a corresponding increase in temperature In the body, water absorbs the heat generated by chemical reactions without greatly increasing in temperature Moreover, when the environmental temperature soars, the water stored in the body helps keep the body cool This cooling effect happens as warm blood from the body’s core flows to the blood vessels just under the skin and is transferred to the environment At the same time, sweat glands release warm water in sweat As the water evaporates into the air, it carries away heat, and then the cooler blood from the periphery circulates back to the body core Water as a Component of Liquid Mixtures A mixture is a combination of two or more substances, each of which maintains its own chemical identity In other words, the constituent substances are not chemically bonded into a new, larger chemical compound The concept is easy to imagine if you think of powdery substances such as flour and sugar; when you stir them together in a bowl, they obviously not bond to form a new compound The room air you breathe is a gaseous mixture, containing three discrete elements—nitrogen, oxygen, and argon—and one compound, carbon dioxide There are three types of liquid mixtures, all of which contain water as a key component These are solutions, colloids, and suspensions For cells in the body to survive, they must be kept moist in a water-based liquid called a solution In chemistry, a liquid solution consists of a solvent that dissolves a substance called a solute An important characteristic of solutions is that they are homogeneous; that is, the solute molecules are distributed evenly throughout the solution If you were to stir a teaspoon of sugar into a glass of water, the sugar would dissolve into sugar molecules separated by water molecules The ratio of sugar to water in the left side of the glass would be the same as the ratio of sugar to water in the right side of the 2/11 Inorganic Compounds Essential to Human Functioning glass If you were to add more sugar, the ratio of sugar to water would change, but the distribution—provided you had stirred well—would still be even Water is considered the “universal solvent” and it is believed that life cannot exist without water because of this Water is certainly the most abundant solvent in the body; essentially all of the body’s chemical reactions occur among compounds dissolved in water Because water molecules are polar, with regions of positive and negative electrical charge, water readily dissolves ...IMPORTING THE LAW IN POST-COMMUNIST TRANSITIONS This book, one of the very first monographs on the Hungarian Constitutional Court available in English, is a unique study of the birth of a new legal system after the collapse of communism in Central and Eastern Europe. It shows that the genesis of the new legal order was determined by massive Western involve- ment and an unprecedented level of exportation and importation of law. Anchored in a detailed comparative study of German and Hungarian constitu- tional case law on human dignity, this book argues that law importation was a deliberate strategy carried out by the Hungarian Court in the early years of its operation. It explains how the circumstances of the transition and the back- ground of the importers determined the choice of German case law as a model and how the Court used it to construct its own version of the right to human dig- nity. It highlights the Hungarian Court’s instrumentalisation of imported law in order to lay the foundations of a new conception of fundamental rights. While focusing on the Hungarian experience, this book engages with international debates and provides an original theoretical framework for approaching the movement of law from the importers’ perspective. Volume 1 in the series, Human Rights Law in Perspective Human Rights Law in Perspective General Editor: Colin Harvey The language of human rights figures prominently in legal and political debates at the national, regional and international levels. In the UK the Human Rights Act 1998 has generated considerable interest in the law of human rights. It will continue to provoke much debate in the legal community and the search for original insights and new materials will intensify. The aim of this series is to provide a forum for scholarly reflection on all aspects of the law of human rights. The series will encourage work which engages with the theoretical, comparative and international dimensions of human rights law. The primary aim is to publish over time books which offer an insight into human rights law in its contextual setting. The objective is to promote an understanding of the nature and impact of human rights law. The series is inclusive, in the sense that all perspectives in legal scholarship are wel- come. It will incorporate the work of new and established scholars. Human Rights Law in Perspective is not confined to consideration of the UK. It will strive to reflect comparative, regional and international perspectives. Work which focuses on human rights law in other states will therefore be included in this series. The intention is to offer an inclusive intellectual home for significant scholarly contributions to human rights law. Volume 1 Importing the Law in Post-Communist Transitions Catherine Dupré Importing the Law in Post-Communist Transitions The Hungarian Constitutional Court and the Right to Human Dignity CATHERINE DUPRÉ OXFORD – PORTLAND OREGON 2003 Hart Publishing Oxford and Portland, Oregon Published in North America (US and Canada) by Hart Publishing c/o International Specialized Book Allosteric modulation of myristate and Mn(III)heme binding to human serum albumin Optical and NMR spectroscopy characterization Gabriella Fanali 1 , Riccardo Fesce 1 , Cristina Agrati 1 , Paolo Ascenzi 2,3 and Mauro Fasano 1 1 Dipartimento di Biologia Strutturale e Funzionale, and Centro di Neuroscienze, Universita ` dell’Insubria, Busto Arsizio (VA), Italy 2 Dipartimento di Biologia, and Laboratorio Interdisciplinare di Microscopia Elettronica, Universita ` ‘Roma Tre’, Italy 3 Istituto Nazionale per le Malattie Infettive I.R.C.C.S. ‘Lazzaro Spallanzani’, Roma, Italy Human serum albumin (HSA) is the most prominent protein in plasma, but it is also found in tissues and secretions throughout the body. HSA abundance (its concentration being 45 mgÆmL )1 in the serum of human adults) contributes significantly to colloid- osmotic blood pressure. HSA, best known for its extraordinary ligand binding capacity, is constituted by a single nonglycosylated all-a chain of 65 kDa con- taining three homologous domains (labelled I, II, and III), each composed of two (A and B) subdomains. The three domains have different binding capacity for a broad variety of ligands such as aminoacids (Trp and Cys), hormones, metal ions, and bilirubin. Moreover, HSA has a high affinity for heme and is Keywords allostery; fatty acid binding; heme binding; human serum albumin; NMR relaxation Correspondence M. Fasano, Dipartimento di Biologia Strutturale e Funzionale, Universita ` dell’Insubria, Via Alberto da Giussano 12, I-21052 Busto Arsizio (VA), Italy Fax: +39 0331 339459 Tel: +39 0331 339450 E-mail: mauro.fasano@uninsubria.it Website: http://fisio.dipbsf.uninsubria.it/cns/ fasano (Received 21 April 2005, revised 25 July 2005, accepted 26 July 2005) doi:10.1111/j.1742-4658.2005.04883.x Human serum albumin (HSA) is best known for its extraordinary ligand binding capacity. HSA has a high affinity for heme and is responsible for the transport of medium and long chain fatty acids. Here, we report myri- state binding to the N and B conformational states of Mn(III)heme–HSA (i.e. at pH 7.0 and 10.0, respectively) as investigated by optical absorbance and NMR spectroscopy. At pH 7.0, Mn(III)heme binds to HSA with lower affinity than Fe(III)heme, and displays a water molecule coordinated to the metal. Myristate binding to a secondary site FAx, allosterically coupled to the heme site, not only increases optical absorbance of Mn(III)heme-bound HSA by a factor of approximately three, but also increases the Mn(III)- heme affinity for the fatty acid binding site FA1 by 10–500-fold. Cooper- ative binding appears to occur at FAx and accessory myristate binding sites. The conformational changes of the Mn(III)heme–HSA tertiary struc- ture allosterically induced by myristate are associated with a noticeable change in both optical absorbance and NMR spectroscopic properties of Mn(III)heme–HSA, allowing the Mn(III)-coordinated water molecule to exchange with the solvent bulk. At pH ¼ 10.0 both myristate affinity for FAx and allosteric modulation of FA1 are reduced, whereas cooperation of accessory sites and FAx is almost unaffected. Moreover, Mn(III)heme binds to HSA with higher affinity than at pH 7.0 even in the absence of myristate, and the metal-coordinated water molecule is displaced. As a whole, these results suggest that FA binding promotes conformational changes reminiscent of N to B state HSA transition, and appear of general significance for a deeper understanding of Nucleotide binding to human UMP-CMP kinase using fluorescent derivatives ) a screening based on affinity for the UMP-CMP binding site Dimitri Topalis 1, *, Hiroki Kumamoto 2, *, Maria-Fernanda Amaya Velasco 3, *, Laurence Dugue ´ 4 , Ahmed Haouz 5 , Julie Anne C. Alexandre 1 , Sarah Gallois-Montbrun 6,† , Pedro Maria Alzari 3 , Sylvie Pochet 4 , Luigi Andre ´ Agrofoglio 2 and Dominique Deville-Bonne 1 1 Laboratoire d’Enzymologie Mole ´ culaire et Fonctionnelle, FRE 2852 CNRS-Paris 6, Institut Jacques Monod, Paris, France 2 Institut de Chimie Organique et Analytique, UMR CNRS 6005, FR 2708, Universite ´ d’Orle ´ ans, UFR Sciences, Orle ´ ans, France 3 Unite ´ de Biochimie Structurale, URA CNRS 2185, Institut Pasteur, Paris, France 4 Unite ´ de Chimie Organique, URA CNRS 2128, Institut Pasteur, Paris, France 5 Plate-Forme 6- Cristalloge ´ ne ` se et Diffraction des Rayons X, Institut Pasteur, Paris, France 6 Unite ´ de Re ´ gulation Enzymatique des Activite ´ s Cellulaires, CNRS URA 2185, Institut Pasteur, Paris, France Human UMP-CMP kinase (UCK) plays a key role in the ribonucleoside and deoxyribonucleoside salvage pathway and in the anabolic phosphorylation of nucleo- side analogs used as antiviral and anticancer agents. The phosphorylation of nucleoside analogs requires three steps involving the action of deoxyribonucleoside kinase Keywords cidofovir; human UMP-CMP kinase; MABA- CDP; Mant-ATP; phosphonates Correspondence D. Deville-Bonne, Laboratoire d’Enzymologie Mole ´ culaire et Fonctionnelle, FRE 2852 CNRS-Paris 6, Institut Jacques Monod, 4, place Jussieu, 75251 Paris Cedex 05, France Fax: +33 1 44 27 59 94 Tel: +33 1 44 27 59 93, E-mail: ddeville@ccr.jussieu.fr *These authors contributed equally to this work  Present address Department of Infectious Diseases, Guy’s, King’s and St Thomas’ Medical School, King’s College London, GKT Guy’s Hospital, London (Received 12 February 2007, revised 25 May 2007, accepted 29 May 2007) doi:10.1111/j.1742-4658.2007.05902.x Methylanthraniloyl derivatives of ATP and CDP were used in vitro as fluorescent probes for the donor-binding and acceptor-binding sites of human UMP-CMP kinase, a nucleoside salvage pathway kinase. Like all NMP kinases, UMP-CMP kinase binds the phosphodonor, usually ATP, and the NMP at different binding sites. The reaction results from an in-line phosphotransfer from the donor to the acceptor. The probe for the donor site was displaced by the bisubstrate analogs of the Ap5X series (where X ¼ U, dT, A, G), indicating the broad specificity of the acceptor site. Both CMP and dCMP were competitors for the acceptor site probe. To find antimetabolites for antivirus and anticancer therapies, we have devel- oped a method of screening acyclic phosphonate analogs that is based on the affinity of the acceptor-binding site of the human UMP-CMP kinase. Several uracil vinylphosphonate derivatives had affinities for human UMP- CMP kinase similar to those of dUMP and dCMP and better than that of cidofovir, an acyclic nucleoside phosphonate with a broad spectrum of antiviral activities. The uracil derivatives were inhibitors rather than substrates of human UMP-CMP kinase. Also, the 5-halogen-substituted analogs inhibited the human TMP kinase less efficiently. The broad speci- ficity of the enzyme acceptor-binding site is in agreement with a large substrate-binding pocket, as shown by the 2.1 A ˚ crystal structure. Abbreviations Ap5A, P 1 -(5¢-adenosyl) Mathematics is essential to progress of human Do you agree that the study of Mathematics is essential to the progress of the human race? Though the study of Mathematics had occupied the attention of Egyptian and Greek scholars centuries ago, yet it was only after the advent of the Industrial Revolution that the importance of the subject was fully realized by scholars and educationists everywhere Today, Mathematics is one of the most important subjects in all the schools and universities of the world Before the Industrial Revolution, men lived very simple lives Agriculture, hunting and fishing were then their main sources of livelihood It did not occur to them that their lives could be made more comfortable if they only exercised their mental faculties a little more and organized a system of knowledge, which we now call the Science, and applied it to practical purposes Thus, they turned to nature for sustenance, and were satisfied with what they could acquire from nature with their skills This simple mode of existence was, however, disturbed by the inventions of a few men, sometime in the eighteenth century, which caused people everywhere to think of new ways of improving their conditions of living The inventions revealed new sources of comfort, and power for the production of goods Thus, the Industrial Revolution began More and more machines were invented for the rapid production of goods, and the study of Mathematics began to receive great encouragement, for it was realized that machines function on mathematical principles The intensive study of Mathematics revealed its potentialities It was soon applied not only to invent new machinery but also to explain abstruse subjects such as Physics, Logic and many others In fact, Mathematics is now used to teach and explain almost every important subject in schools and universities Even the construction of buildings and bridges requires a deep knowledge of Mathematics The study of Mathematics has also helped to increase the mental powers of men They are not only able to think more clearly than they could before but are also able to understand and explain many of the things which they could not understand earlier Sometimes, however, Mathematical principles have been applied for tragic consequences In battles and wars, bombs and cannon-balls have been released with remarkable accuracy to destroy the enemy This fact reveals how knowledge of Mathematics could be used to hinder human process But such a situation develops only when men have lost their patience and their capacity for compromise and fortunately the leaders of the world today are trying their utmost to remove the causes for war In general, however, men have a natural impulse to live in peace and harmony with others, and almost every invention is aimed at promoting the welfare of the people of the world Thus, the human race has benefited from the efforts of those who have made the fullest use of Mathematical principles for all their inventions I therefore agree that the study of Mathematics is essential to the progress of the human race Toán học điều cần thiết để tiến người Bạn có đồng ý nghiên cứu Toán học điều cần thiết cho tiến nhân loại? Mặc dù nghiên cứu Toán học chiếm ý học giả Ai Cập Hy Lạp kỷ trước, sau đời Cách mạng công nghiệp mà tầm quan trọng đối tượng nhận thức đầy đủ học giả nhà giáo dục khắp nơi Hôm nay, Toán học môn học quan trọng tất trường học trường đại học giới Trước Cách mạng Công nghiệp, người đàn ông có sống đơn giản Nông nghiệp, săn bắn câu cá sau nguồn họ sinh kế Nó không xảy với họ sống họ thoải mái họ thực lực tinh thần họ nhiều chút có tổ chức hệ thống tri thức, mà gọi khoa học, áp dụng vào mục đích thực tế Vì vậy, họ tìm đến thiên nhiên cho thức ăn, hài lòng với họ có từ thiên nhiên với kỹ họ Đây chế độ đơn giản tồn được, nhiên, bị quấy rầy phát minh vài người đàn ông, kỷ thứ mười tám, khiến người khắp nơi để nghĩ cách việc cải thiện điều kiện sống họ Những phát minh tiết lộ nguồn thoải mái, quyền ... as the ratio of sugar to water in the right side of the 2/11 Inorganic Compounds Essential to Human Functioning glass If you were to add more sugar, the ratio of sugar to water would change,... is critical, because fluctuations—either too acidic or too alkaline—can lead to life-threatening disorders 8/11 Inorganic Compounds Essential to Human Functioning All cells of the body depend... called acetate after it gives up a proton Acids and Bases 6/11 Inorganic Compounds Essential to Human Functioning (a) In aqueous solution, an acid dissociates into hydrogen ions (H+) and anions Nearly