DOCSLIB.ORG

Chem331 Tansey Chpt3

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Chem331 Tansey Chpt3 1/21/20 Isoelectric Points O R + H3N C CH NH COO- CH NH C If the side group is not ionizable, then the pI is the average of the CH C and N groups pKa R O R Calculations of pI for a compound with more than two dissociable groups carries more possibility for error Each amino acid is called a residue First write out all possible ionic structures for a compound in order that they occur starting with the most basic to the most acidic Addition of acid or base hydrolyzes the peptide Next, identify the isoionic, zwiterionic or neutral representation - The pI is the pH at the midpoint between the pK values on bond and adds water back across the peptide either side of the isoionic species bond. What about peptides or proteins? The amino (N) terminal is written on the left and the carboxyl (C) terminal is on the right. The Peptide Bond Peptide Bond O R H N COO- + 3 C CH NH CH NH C CH R O R – Rx of bond formation costs energy (ATP) but degradation of • has partial (40%) double bond character proteins is thermodynamically favorable. (entropy) • N partially positive; O partially negative – C-N bond shorter than normal and more like double bond • has a length of about 0.133 nm - shorter than a typical – R groups usually found in the trans conformation single bond but longer than a double bond – This results in rigid planar, non-rotating links between aa • Due to the double-bond character of the peptide bond, the – Size of peptides and proteins are described in Daltons six atoms of the peptide bond group define a plane – the – 1 atomic unit = 1 dalton ; MW = Dalton / kd; amide plane Mr=molecular weight Fundamental Structural The Peptide Bond Pattern in Proteins Size of R groups may favor/disfavor cis- peptide bond The peptide bond is best described as a resonance hybrid The trans conformation of the forms shown on the two previous slides. of the peptide bond. The cis-peptide bond 1 1/21/20 Fundamental Structural Peptide Backbone Pattern in Proteins Rotatable peptide bonds • Due to peptide bond (review) • Trans conformation of a carbon is more stable and primary conformation • Consider the consequence of this arraignment • 10% of Pro are in Cis. Peptide Backbone Limited rotation around a carbon • Dihedral/torsion angles describe the rotation around the a carbon • C-N Phi and C-C Psi • The peptide bond is creates limited possibilities. • Torsion angles are defined by 4 points or planes • Notice the side groups When proline is in a peptide bond, it does not have a hydrogen on the α amino group, so it cannot donate a hydrogen bond to stabilize an α helix or a β sheet. Many peptides have important Peptide Backbone biological activities Limited Options Insulin - Short peptide produced as a pre-pro-peptide. The • Peptide bond limits rotation along all initial peptide is much longer and is modified twice, each time bonds in backbone creating a a set of peptide bonds are hydrolyzed. The final shortened • 3D spatial arrangement is determined version is active. There are two subunits, held together by a by the limited rotational options disulfide bond. • R groups add limitations – steric • Amide H and Carbonyl O also impact rotation options • R groups have NOTHING to do with peptide bond issue 2 1/21/20 Structure of Insulin Insulin Primary structure tells of relatedness The inactive insulin is a hexamer, where via processing it loses the metal ion and is converted to an active monomer Differences of one or two amino acids make the peptide more immunoreactive (allergenic) to some Change affinity for Gluten – a tale of two receptor proteins Glutenin – Long and very large proteins which have lots of sulfur atoms. Coiled proteins which can stretch and recoil. Sulfur Long-Acting Fast -Acting (cystine side chains) help hold these together Gliadins – Smaller proteins which act like Fast-acting insulin is usually taken just after or before meals for controlling blood sugar spikes. It often begins to work in 10 to 15 lubricants or ball bearings – allowing parts of minutes, peaks in about 1 hour, and lasts for about 3 to 5 hours. glutenins to move past each other Long-acting insulin begins action after 1 to 2 hours. Its insulin effect plateaus for the next few hours and then a relatively flat action duration follows, and this lasts for about 15 to 24 hours. Dough Strength = Gluten Formation Glialdin Glutenin Raw un-worked dough Stretched and kneaded dough Loose structure – no gluten Elastic and strong structure = gluten Coils and sulfur cross-links (black lines) of glutenin give the elastic ability to dough • High protein (and gluten) flour give strong gas pockets good for breads • Low gluten flours are weaker tender baked goods – cakes and cookies (that is why you don’t over mix pancake mix) • High water dough (called batter) dilutes gluten so they don’t mix/bind - Click here to explore Gluten 3 1/21/20 Amino Acids Give Why so many Glutamines? Function Glutamine supplies N for growing seedling. ALSO Glutamine side chains (amine) can hydrogen bond with another glutamine forming a crosslink between strands of glutenin • If there were less glutamines, the amine The protein sequence in single letter amino acid would bind to water abbreviations for glutenin. Notice the high proportion of instead reducing Q & P (highlighted in dark shading) and the low cross-linked strength abundance of charged D & E (Shaded in light color) Proline What about Cysteines? Up to 50% of amino acids of glutenin can be proline – typical protein is ten to 20 times lower • Prolines are the most inflexible amino acids and in a peptide / protein backbone lead to bends and kinks Two cysteine amino acids bond forming a disulfide – a cross- breaking up helixes started by glutamine linked glutenin is more stable and mechanically rigid • This gives glutenin its elasticity Strengthen your flour Bioactive Peptides muscle Oxytocin and Vasopressin – Start as long precursors in hypothalamus- whose final form is 9 aa Oxidizing agents – alter sulfur links and increases – differ by 2 residues • oxytocin - uterine contraction during childbirth and milk production strengths of gluten during lactation • Flowing oxygen gas through the flour “ages” it by • vasopressin - alters blood pressure by forcing kidney to retain water, allowing sulfur-sulfur links to form – giving more increasing the volume of blood cross-links (stronger flour) Met-enkephalin (opioid peptides) • Chlorine gas and brominates (can do same thing) but » Naturally produced peptides, bind to receptors, and reduce no longer approved pain cause pleasure. Morphine like • Ascorbic acid (vitamin C) is now used instead of Substance P » Opposite effect from opioids gasses. » Stimulates perception of pain (protective mechanism) • Also causes the flour to whiten (bleaching) 4 1/21/20 Proteins: Three- dimensional structure Cofactors Defined Background on protein composition: Cofactors are nonprotein Two general classes of proteins groups required for protein • Fibrous - long rod-shaped, insoluble proteins. These proteins are strong binding or activity. (high tensile strength). Examples: keratin, hair, collagen, skin nails etc… • Globular - compact spherical shaped proteins usually water-soluble. Most – Can be divided into two hydrophobic amino acids found in the interior away from the water. Nearly categories: minerals all enzymes are globular… an example is hemoglobin (metal ions) and vitamins Proteins can be simple - no added groups or modifications, just amino acids (small organic groups) – Metal ions (Ca2+, Mg2+, Or proteins can be conjugated. Additional groups covalently bound to the Zn2+, Fe2+, and Cu2+) amino acids. The naked protein is called the apoprotein and the added group is the prosthetic group. Together the protein and prosthetic group is – Organic groups (NAD+ called the holoprotein. Ex. Hemoglobin and FAD, pyridoxal phosphate) Levels of Structure Primary Structure Type of Structure: Defines: Type of Bonds: Primary (1°) Order of amino acids Covalent bonds Secondary (2°) Local structure Non-covalent The order of the 20 common amino acids is the primary (α-helix, β-sheet, loop) interactions, disulfides structure Tertiary (3°) Overall fold, 2° Non-covalent elements organize and interactions, disulfides - shape, orientation and other information is not part of the compact—low surface primary structure to volume ratio - Primary structure is informative for determining - Relativeness to other proteins or regions of proteins Quaternary (4°) Subunit organization, Non-covalent - Predict structure dimers, macro- interactions, disulfides - Determine domain (group of aa that has a function) molecular assembly - Predict RNA and DNA sequence Secondary Structure α-helix Primary Secondary/Tertiary FUNCTION! Discovered by Linus Pauling Structure Structure •2 Nobel prizes. •Discovered folding while sick in bed! Protein structure is defined by the •Treated poorly as a result of his anti-nuclear nd peptide plane and the 2 degrees of stands - 2 NB prize freedom around the peptide bond • The helix is a right handed twist of the backbone - Two basic predictable forms of notice when we are looking at this the side groups secondary structure are NOT considered Alpha helix and beta pleated sheet • Notice where the amino acids are. • Hydrogen bonding occurs between the carbonyl -Other forms are specialized and the amino group ~four residues away (3.6 aa/turn). The bonding takes place within the same (collagen) chain. i+4 - Beta sheets, tight turns and beta bulge A run of proline residues lead to breaking the helix structure. Why? 5 1/21/20 α-helix α-helix Formation of α-helices are governed by HYDROGEN For an a-helix of n residues, BONDS! One helix turn is 3.6 amino there are n-4 hydrogen acid residues, and involves bonds! 13 atoms from the O to the H Helix capping—the last 4 of the H bond amide hydrogens/carbonyl 13 oxygens cannot H-bond.
Load more

Recommended publications
  • The Future of Protein Secondary Structure Prediction Was Invented by Oleg Ptitsyn
    biomolecules Review The Future of Protein Secondary Structure Prediction Was Invented by Oleg Ptitsyn 1, 1, 1 2 1,3 Daniel Rademaker y, Jarek van Dijk y, Willem Titulaer , Joanna Lange , Gert Vriend and Li Xue 1,* 1 Centre for Molecular and Biomolecular Informatics (CMBI), Radboudumc, 6525 GA Nijmegen, The Netherlands; [email protected] (D.R.); [email protected] (J.v.D.); [email protected] (W.T.); [email protected] (G.V.) 2 Bio-Prodict, 6511 AA Nijmegen, The Netherlands; [email protected] 3 Baco Institute of Protein Science (BIPS), Mindoro 5201, Philippines * Correspondence: [email protected] These authors contributed equally to this work. y Received: 15 May 2020; Accepted: 2 June 2020; Published: 16 June 2020 Abstract: When Oleg Ptitsyn and his group published the first secondary structure prediction for a protein sequence, they started a research field that is still active today. Oleg Ptitsyn combined fundamental rules of physics with human understanding of protein structures. Most followers in this field, however, use machine learning methods and aim at the highest (average) percentage correctly predicted residues in a set of proteins that were not used to train the prediction method. We show that one single method is unlikely to predict the secondary structure of all protein sequences, with the exception, perhaps, of future deep learning methods based on very large neural networks, and we suggest that some concepts pioneered by Oleg Ptitsyn and his group in the 70s of the previous century likely are today’s best way forward in the protein secondary structure prediction field.
    [Show full text]
  • Amino Acid Building Block Models – in Brief
    Amino Acid Building Block Models – In Brief Key Teaching Points for Amino Acid Building Block Models© Overall Student Learning Objective: What Dictates How a Protein Folds? Amino acids are the building blocks of proteins. All amino acids have an identical core structure consisting of an alpha-carbon, carboxyl group, amino group and R-group (sidechain). A linear chain of amino acids is a polypeptide. The primary sequence of a protein is the linear sequence of amino acids in a polypeptide. Proteins are made up of amino acid monomers linked together by peptide bonds. Peptide bond formation between amino acids results in the release of water (dehydration synthesis or condensation reaction). The protein backbone is characterized by the “N-C-C-N-C-C. .” pattern. The “ends” of the protein can be identified by the N-terminus (amino group) end and the C-terminus (carboxyl group) end. For a more complete lesson guide, please visit: http://www.3dmoleculardesigns.com/3DMD-Files/AABB/ContentsandAssembly.pdf Amino Acid Core Structure Build an amino acid according to the diagram to the right: 1. Identify the alpha carbon, amino group, carboxyl group and R-group (sidechain representation) in the structure you have constructed. Two amino acids can be chemically linked by a reaction called “condensation” or “dehydration synthesis” to form a dipeptide bond linking the two amino acids. A chain of amino acid units (monomers) linked together by peptide bonds is called a polypeptide. General Dipeptide Structure Construct a model of a dipeptide using the amino acid models previously built. 2. What are the products of the condensation reaction (dehydration synthesis)? 3.
    [Show full text]
  • Chapter 4 the Three-Dimensional Structure of Proteins
    Chapter 4 The Three-Dimensional Structure of Proteins Multiple Choice Questions 1. Answer: D All of the following are considered “weak” interactions in proteins, except: A) hydrogen bonds. B) hydrophobic interactions. C) ionic bonds. D) peptide bonds. E) van der Waals forces. 2. Answer: D In an aqueous solution, protein conformation is determined by two major factors. One is the formation of the maximum number of hydrogen bonds. The other is the: A) formation of the maximum number of hydrophilic interactions. B) maximization of ionic interactions. C) minimization of entropy by the formation of a water solvent shell around the protein. D) placement of hydrophobic amino acid residues within the interior of the protein. E) placement of polar amino acid residues around the exterior of the protein. 3. 3 Answer: A In the diagram below, the plane drawn behind the peptide bond indicates the: A) absence of rotation around the C—N bond because of its partial double-bond character. B) plane of rotation around the C—N bond. C) region of steric hindrance determined by the large C=O group. D) region of the peptide bond that contributes to a Ramachandran plot. E) theoretical space between –180 and +180 degrees that can be occupied by the and angles in the peptide bond. 4. Answer: D Which of the following best represents the backbone arrangement of two peptide bonds? A) C—N—C—C—C—N—C—C B) C—N—C—C—N—C C) C—N—C—C—C—N D) C—C—N—C—C—N Chapter 4 The Three-Dimensional Structure of Proteins E) C—C—C—N—C—C—C 5.
    [Show full text]
  • Conformational Properties of Constrained Proline Analogues and Their Application in Nanobiology”
    UNIVERSITAT POLITÈCNICA DE CATALUNYA DEPARTAMENT D’ENGINYERIA QUÍMICA “CONFORMATIONAL PROPERTIES OF CONSTRAINED PROLINE ANALOGUES AND THEIR APPLICATION IN NANOBIOLOGY” Alejandra Flores Ortega Supervisors: Dr. Carlos Alemán Llansó and Dr. Jordi Casanovas Salas. th Barcelona, 27 January 2009 “Chance is a word void of sense; nothing can exist without a cause”. François-Marie Arouet, Voltaire “Imagination will often carry us to worlds that never were. But without it, we go nowhere”. Carl Sagan iii ACKNOWLEDGEMENTS I would like to acknowledge to Dr. Carlos Aleman and Dr. Jordi Cassanovas Salas for an interesting research theme, and scientific support. I gratefully acknowledge to Dr. David Zanuy for interesting suggestions and strong discussions, without their support this would be an unfulfilled task. Also I, would like to address my thanks to all my colleagues in my group and department, specially Elaine Armelin for assiting me in many different ways. I thank not only my friends, but also colleagues for helping me to overcome the stressful time, without whom it would have been difficult to cope up. I wish to express my gratefulness to my parents, specially to my mother, María Esther, for all his care, and support. Also I will like to thanks to my friends and specially Jesus, Merches, Laura y Arturo. My PhD thesis have been finished for all this support. I am greatly indepted to Dr. Ruth Nussinov at NCI, Dr. Carlos Cativiela at the University of Zaragoza and Ana I. Jiménez at the “Instituto de Ciencias de Materiales de Aragon” for a collaborative effort. I wish to thank all my colleague in the “Chimie et Biochimie Théoriques, Faculté des Sciences et Techniques” in Nancy France, I will be grateful to have worked with : Pr.
    [Show full text]
  • 2. Proteins Have Hierarchies of Structure
    27 2. Proteins have Hierarchies of Structure Protein structure is usually described at four different levels (Fig. II.2.1). The first level, called the primary structure, describes the linear sequence of the amino acids in the chain. The different primary structures correspond to the different sequences in which the amino acids are covalently linked together. The secondary structure describes two common patterns of structural repetition in proteins: the coiling up into helices of segments of the chain, and the pairing together of strands of the chain into β-sheets. The tertiary structure is the next higher level of organization, the overall arrangement of secondary structural elements. The quaternary structure describes how different polypeptide chains are assembled into complexes. Figure II.2.1. Different levels of protein structure. A protein chain’s primary structure is its amino acid sequence. Secondary structure consists of the regular organization of helices and sheets. The example shown is a schematic representation of an α helix. Tertiary structure is a polypeptide chain’s three- dimensional native conformation, which often involves compact packing of secondary structure elements. The example given in the figure is a schematic drawing of one of the four polypeptide chains (subunits) of hemoglobin, the protein that transports oxygen in the blood. α-helices along the chain are represented as cylinders. N is the amino terminus and C is the carboxyl terminus of the polypeptide chain. Quaternary structure is the arrangement of multiple polypeptide chains (subunits) to form a functional biomolecular structure. The figure shows the quaternary arrangement of four subunits to form the functional hemoglobin molecule.
    [Show full text]
  • Introduction to Proteins and Amino Acids Introduction
    Introduction to Proteins and Amino Acids Introduction • Twenty percent of the human body is made up of proteins. Proteins are the large, complex molecules that are critical for normal functioning of cells. • They are essential for the structure, function, and regulation of the body’s tissues and organs. • Proteins are made up of smaller units called amino acids, which are building blocks of proteins. They are attached to one another by peptide bonds forming a long chain of proteins. Amino acid structure and its classification • An amino acid contains both a carboxylic group and an amino group. Amino acids that have an amino group bonded directly to the alpha-carbon are referred to as alpha amino acids. • Every alpha amino acid has a carbon atom, called an alpha carbon, Cα ; bonded to a carboxylic acid, –COOH group; an amino, –NH2 group; a hydrogen atom; and an R group that is unique for every amino acid. Classification of amino acids • There are 20 amino acids. Based on the nature of their ‘R’ group, they are classified based on their polarity as: Classification based on essentiality: Essential amino acids are the amino acids which you need through your diet because your body cannot make them. Whereas non essential amino acids are the amino acids which are not an essential part of your diet because they can be synthesized by your body. Essential Non essential Histidine Alanine Isoleucine Arginine Leucine Aspargine Methionine Aspartate Phenyl alanine Cystine Threonine Glutamic acid Tryptophan Glycine Valine Ornithine Proline Serine Tyrosine Peptide bonds • Amino acids are linked together by ‘amide groups’ called peptide bonds.
    [Show full text]
  • Detection of Trans-Cis Flips and Peptide-Plane Flips in Protein Structures
    research papers Detection of trans–cis flips and peptide-plane flips in protein structures ISSN 1399-0047 Wouter G. Touw,a* Robbie P. Joostenb and Gert Vrienda* aCentre for Molecular and Biomolecular Informatics, Radboud University Medical Center, Geert Grooteplein-Zuid 26-28, 6525 GA Nijmegen, The Netherlands, and bDepartment of Biochemistry, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. *Correspondence e-mail: [email protected], Received 4 February 2015 [email protected] Accepted 27 April 2015 A coordinate-based method is presented to detect peptide bonds that need Edited by G. J. Kleywegt, EMBL–EBI, Hinxton, correction either by a peptide-plane flip or by a trans–cis inversion of the peptide England bond. When applied to the whole Protein Data Bank, the method predicts 4617 trans–cis flips and many thousands of hitherto unknown peptide-plane flips. Keywords: peptide conformation; cis peptide A few examples are highlighted for which a correction of the peptide-plane bond; structure validation; structure correction. geometry leads to a correction of the understanding of the structure–function relation. All data, including 1088 manually validated cases, are freely available and the method is available from a web server, a web-service interface and through WHAT_CHECK. 1. Introduction Peptide bonds connect adjacent amino acids in proteins. The partial double-bond character of the peptide bond restricts its torsion. The dihedral angle ! (CiÀ1—CiÀ1—Ni—Ci ) typically has values around 180 (trans)or0 (cis), although exceptions are possible (Berkholz et al., 2012). The Ci–1—Ci distance is around 3.81 A˚ in the trans conformation and around 2.94 A˚ in the cis conformation.
    [Show full text]
  • The Α-Helix Forms Within a Continuous Strech of the Polypeptide Chain
    The α-helix forms within a continuous strech of the polypeptide chain N-term prototypical φ = -57 ° ψ = -47 ° 5.4 Å rise, 3.6 aa/turn ∴ 1.5 Å/aa C-term α-Helices have a dipole moment, due to unbonded and aligned N-H and C=O groups β-Sheets contain extended (β-strand) segments from separate regions of a protein prototypical φ = -139 °, ψ = +135 ° prototypical φ = -119 °, ψ = +113 ° (6.5Å repeat length in parallel sheet) Antiparallel β-sheets may be formed by closer regions of sequence than parallel Beta turn Figure 6-13 The stability of helices and sheets depends on their sequence of amino acids • Intrinsic propensity of an amino acid to adopt a helical or extended (strand) conformation The stability of helices and sheets depends on their sequence of amino acids • Intrinsic propensity of an amino acid to adopt a helical or extended (strand) conformation The stability of helices and sheets depends on their sequence of amino acids • Intrinsic propensity of an amino acid to adopt a helical or extended (strand) conformation • Interactions between adjacent R-groups – Ionic attraction or repulsion – Steric hindrance of adjacent bulky groups Helix wheel The stability of helices and sheets depends on their sequence of amino acids • Intrinsic propensity of an amino acid to adopt a helical or extended (strand) conformation • Interactions between adjacent R-groups – Ionic attraction or repulsion – Steric hindrance of adjacent bulky groups • Occurrence of proline and glycine • Interactions between ends of helix and aa R-groups His Glu N-term C-term
    [Show full text]
  • Introduction 1.1 Post-Translational Modifications
    Chapter I: Introduction 1.1 Post-translational modifications Post-translational modifications (PTMs) are responsible for dynamic regulation of protein structure and function (Jensen et al., 2006). One example of the function of post-translational modifications in the dynamic regulation of protein structure and function is signal transduction; post-translational modification of key regulatory proteins in signal transduction pathways controls cellular proliferation, metabolism, gene expression, cytoskeletal organization and apoptosis (Jensen et al., 2006). Post-translational modifications not only change the mass of the protein, they are also often responsible for changes in charge, structure and conformation. This leads to changes in the biological activity of proteins like enzymes, the binding affinity of proteins to receptors and other protein-protein interactions (Hoffmann et al., 2008) (Murray et al., 1998). For example, the interaction of the cytokine TGF-beta with its receptor complex results in the phosphorylation of SMAD family proteins which activates these proteins to regulate target gene expression (Massague et al., 2000). Post-translational modified amino acid residues can act as binding sites on proteins for a specific recognition domain on other proteins. For example, phosphorylated tyrosine residues can bind to SH2 or PTB domains (Pawson et al., 1997). Depending on the type of PTM they can be very abundant and have a large number of target proteins, whereas other PTM`s have only a few target proteins. Moreover, some PTM`s are connected with several different residues and not only with one residue. For example multi-site phosphorylation that primarily targets Serine, Threonine and Tyrosine residues is a crucial mechanism for the regulation of protein localization and functional activity (Cohen et al., 2000).
    [Show full text]
  • Peptides & Proteins
    Peptides & Proteins (thanks to Hans Börner) 1 Proteins & Peptides Proteuos: Proteus (Gr. mythological figure who could change form) proteuo: „"first, ref. the basic constituents of all living cells” peptos: „Cooked referring to digestion” Proteins essential for: Structure, metabolism & cell functions 2 Bacterium Proteins (15 weight%) 50% (without water) • Construction materials Collagen Spider silk proteins 3 Proteins Structural proteins structural role & mechanical support "cell skeleton“: complex network of protein filaments. muscle contraction results from action of large protein assemblies Myosin und Myogen. Other organic material (hair and bone) are also based on proteins. Collagen is found in all multi cellular animals, occurring in almost every tissue. • It is the most abundant vertebrate protein • approximately a quarter of mammalian protein is collagen 4 Proteins Storage Various ions, small molecules and other metabolites are stored by complexation with proteins • hemoglobin stores oxygen (free O2 in the blood would be toxic) • iron is stored by ferritin Transport Proteins are involved in the transportation of particles ranging from electrons to macromolecules. • Iron is transported by transferrin • Oxygen via hemoglobin. • Some proteins form pores in cellular membranes through which ions pass; the transport of proteins themselves across membranes also depends on other proteins. Beside: Regulation, enzymes, defense, functional properties 5 Our universal container system: Albumines 6 zones: IA, IB, IIA, IIB, IIIA, IIIB; IIB and
    [Show full text]
  • And Beta-Helical Protein Motifs
    Soft Matter Mechanical Unfolding of Alpha- and Beta-helical Protein Motifs Journal: Soft Matter Manuscript ID SM-ART-10-2018-002046.R1 Article Type: Paper Date Submitted by the 28-Nov-2018 Author: Complete List of Authors: DeBenedictis, Elizabeth; Northwestern University Keten, Sinan; Northwestern University, Mechanical Engineering Page 1 of 10 Please doSoft not Matter adjust margins Soft Matter ARTICLE Mechanical Unfolding of Alpha- and Beta-helical Protein Motifs E. P. DeBenedictis and S. Keten* Received 24th September 2018, Alpha helices and beta sheets are the two most common secondary structure motifs in proteins. Beta-helical structures Accepted 00th January 20xx merge features of the two motifs, containing two or three beta-sheet faces connected by loops or turns in a single protein. Beta-helical structures form the basis of proteins with diverse mechanical functions such as bacterial adhesins, phage cell- DOI: 10.1039/x0xx00000x puncture devices, antifreeze proteins, and extracellular matrices. Alpha helices are commonly found in cellular and extracellular matrix components, whereas beta-helices such as curli fibrils are more common as bacterial and biofilm matrix www.rsc.org/ components. It is currently not known whether it may be advantageous to use one helical motif over the other for different structural and mechanical functions. To better understand the mechanical implications of using different helix motifs in networks, here we use Steered Molecular Dynamics (SMD) simulations to mechanically unfold multiple alpha- and beta- helical proteins at constant velocity at the single molecule scale. We focus on the energy dissipated during unfolding as a means of comparison between proteins and work normalized by protein characteristics (initial and final length, # H-bonds, # residues, etc.).
    [Show full text]
  • Structure and Synthesis of Antifungal Disulfide
    microorganisms Review Structure and Synthesis of Antifungal Disulfide β-Strand Proteins from Filamentous Fungi Györgyi Váradi 1,*, Gábor K. Tóth 1,2 and Gyula Batta 3 1 Department of Medical Chemistry, Faculty of Medicine, University of Szeged, H-6720 Szeged, Hungary; [email protected] 2 MTA-SZTE Biomimetic Systems Research Group, University of Szeged, H-6720 Szeged, Hungary 3 Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary; [email protected] * Correspondence: [email protected]; Tel.: +36-62-545-142; Fax: +36-62-545-971 Received: 20 November 2018; Accepted: 24 December 2018; Published: 27 December 2018 Abstract: The discovery and understanding of the mode of action of new antimicrobial agents is extremely urgent, since fungal infections cause 1.5 million deaths annually. Antifungal peptides and proteins represent a significant group of compounds that are able to kill pathogenic fungi. Based on phylogenetic analyses the ascomycetous, cysteine-rich antifungal proteins can be divided into three different groups: Penicillium chrysogenum antifungal protein (PAF), Neosartorya fischeri antifungal protein 2 (NFAP2) and “bubble-proteins” (BP) produced, for example, by P. brevicompactum. They all dominantly have β-strand secondary structures that are stabilized by several disulfide bonds. The PAF group (AFP antifungal protein from Aspergillus giganteus, PAF and PAFB from P. chrysogenum, Neosartorya fischeri antifungal protein (NFAP)) is the best characterized with their common β-barrel tertiary structure. These proteins and variants can efficiently be obtained either from fungi production or by recombinant expression. However, chemical synthesis may be a complementary aid for preparing unusual modifications, e.g., the incorporation of non-coded amino acids, fluorophores, or even unnatural disulfide bonds.
    [Show full text]