| 19-Aug-2008 |
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Contents
Chapter 1: From Sequence to Structure [PDF] 1-0 Overview: Protein Function and Architecture [Full Text] [PDF] -Proteins are the most versatile macromolecules of the cell -There are four levels of protein structure 1-1 Amino Acids [Full Text] [PDF] -The chemical characters of the amino-acid side chains have important consequences for the way they participate in the folding and functions of proteins 1-2 Genes and Proteins [Full Text] [PDF] -There is a linear relationship between the DNA base sequence of a gene and the amino-acid sequence of the protein it encodes -The organization of the genetic code reflects the chemical grouping of the amino-acids 1-3 The Peptide Bond [Full Text] [PDF] -Proteins are linear polymers of amino acids connected by amide bonds -The properties of the peptide bond have important effects on the stability and flexibility of polypeptide chains in water 1-4 Bonds that Stabilize Folded Proteins [Full Text] [PDF] -Folded proteins are stabilized mainly by weak noncovalent interactions -The hydrogen-bonding properties of water have important effects on protein stability 1-5 Importance and Determinants of Secondary Structure [Full Text] [PDF] -Folded proteins have segments of regular conformation -The arrangement of secondary structure elements provides a convenient way of classifying types of folds -Steric constraints dictate the possible types of secondary structure -The simplest secondary structure element is the beta turn 1-6 Properties of the Alpha Helix [Full Text] [PDF] -Alpha helices are versatile cylindrical structures stabilized by a network of backbone hydrogen bonds -Alpha helices can be amphipathic, with one polar and one nonpolar face -Collagen and polyproline helices have special properties 1-7 Properties of the Beta Sheet [Full Text] [PDF] -Beta sheets are extended structures that sometimes form barrels -Amphipathic beta sheets are found on the surfaces of proteins 1-8 Prediction of Secondary Structure [Full Text] [PDF] -Certain amino acids are more usually found in alpha helices, others in beta sheets 1-9 Folding [Full Text] [PDF] -The folded structure of a protein is directly determined by its primary structure -Competition between self-interactions and interactions with water drives protein folding -Computational prediction of folding is not yet reliable -Helical membrane proteins may fold by condensation of preformed secondary structure elements in the bilayer 1-10 Tertiary Structure [Full Text] [PDF] -The condensing of multiple secondary structural elements leads to tertiary structure -Bound water molecules on the surface of a folded protein are an important part of the structure -Tertiary structure is stabilized by efficient packing of atoms in the protein interior 1-11 Membrane Protein Structure [Full Text] [PDF] -The principles governing the structures of integral membrane proteins are the same as those for water-soluble proteins and lead to formation of the same secondary structure elements 1-12 Protein Stability: Weak Interactions and Flexibility [Full Text] [PDF] -The folded protein is a thermodynamic compromise -Protein structure can be disrupted by a variety of agents -The marginal stability of protein tertiary structure allows proteins to be flexible 1-13 Protein Stability: Post-Translational Modifications [Full Text] [PDF] -Covalent bonds can add stability to tertiary structure -Post-translational modification can alter both the tertiary structure and the stability of a protein 1-14 The Protein Domain [Full Text] [PDF] -Globular proteins are composed of structural domains -Domains have hydrophobic cores -Multidomain proteins probably evolved by the fusion of genes that once coded for separate proteins 1-15 The Universe of Protein Structures [Full Text] [PDF] -The number of protein folds is large but limited -Protein structures are modular and proteins can be grouped into families on the basis of the domains they contain -The modular nature of protein structure allows for sequence insertions and deletions 1-16 Protein Motifs [Full Text] [PDF] -Protein motifs may be defined by their primary sequence or by the arrangement of secondary structure elements -Identifying motifs from sequence is not straightforward 1-17 Alpha Domains and Beta Domains [Full Text] [PDF] -Protein domains can be classified according to their secondary structural elements -Two common motifs for alpha domains are the four-helix bundle and the globin fold -Beta domains contain strands connected in two distinct ways -Antiparallel beta sheets can form barrels and sandwiches 1-18 Alpha/Beta, Alpha+Beta and Cross-Linked Domains [Full Text] [PDF] -In alpha/beta domains each strand of parallel beta sheet is usually connected to the next by an alpha helix -There are two major families of alpha/beta domains: barrels and twists -Alpha+beta domains have independent helical motifs packed against a beta sheet -Metal ions and disulfide bridges form cross-links in irregular domains 1-19 Quaternary Structure: General Principles [Full Text] [PDF] -Many proteins are composed of more than one polypeptide chain -All specific intermolecular interactions depend on complementarity 1-20 Quaternary Structure: Intermolecular Interfaces [Full Text] [PDF] -All types of protein-stabilizing interactions contribute to the formation of intermolecular interfaces -Inappropriate quaternary interactions can have dramatic functional consequences 1-21 Quaternary Structure: Geometry [Full Text] [PDF] -Protein assemblies built of identical subunits are usually symmetric 1-22 Protein Flexibility [Full Text] [PDF] -Proteins are flexible molecules -Conformational fluctuations in domain structure tend to be local -Protein motions involve groups of non-bonded as well as covalently bonded atoms -Triggered conformational changes can cause large movements of side chains, loops, or domains Updates – 2007-2008 Back to top Active transport proteins U1-12 Active Transport: ATP-Binding Cassette Transporters [Full Text] [PDF] -The energy of ATP hydrolysis can be used to pump substrates across membranes -ABC transporters transport an enormous variety of substrates -The nucleotide-binding domain of the ABC transporters dimerizes to bind ATP -The ABC transporters may work by a mechanism of alternating conformational states similar to that of the MFS transporters U1-13 Active Transport: Bacterial Multidrug Resistance [Full Text] [PDF] -Bacteria contain secondary active transporters that pump drugs out of the cell in exchange for the inward transport of protons -In complex with substrate, AcrB is an asymmetrical trimer -RMD proteins appear to operate by a proton-driven alternating-access mechanism Updates – 2006-2007 Back to top Membrane proteins U1-6 Membrane Protein Structure and Function [Full Text] [PDF] -Membrane proteins are essential for intercellular communication, cellular recognition, and the uptake of nutrients -The structures of membrane proteins are slowly being determined U1-7 Membrane Proteins: Topology [Full Text] [PDF] -Aromatic residues in transmembrane proteins are concentrated in a belt at the interface with membrane lipid head-groups -Alpha-helical membrane proteins are inserted into membranes in a variety of orientations U1-8 Membrane-Associated Enzymes [Full Text] [PDF] -The catalytic domains of most membrane-associated enzymes lie outside the lipid bilayer -Membrane-anchored enzymes can be attached to the membrane in different ways -Some enzymes have their catalytic domains inside the membrane bilayer U1-9 Ion Channels: Potassium Ion Channels [Full Text] [PDF] -Ion channels enable charged species to flow into and out of the cell across the hydrophobic lipid bilayer -The opening of most potassium channels is rapid, selective and regulated -Potassium channels contain a selectivity filter -The opening and closing of ion channels is regulated in three different ways U1-10 Pore-Forming Channel Proteins [Full Text] [PDF] -Many neutral substances diffuse across membranes through pores -Aquaporin pore size and polarity discriminate between water and protons -Some pore-forming proteins are toxic to cells U1-11 Active Transport: Major Facilitator Superfamily Transporters [Full Text] [PDF] -Major facilitator superfamily transporters utilize ion gradients to move substrates across membranes -MFS transporters share a common fold -The glycerol-3-phosphate transporter uses ligand-induced conformational changes to move its substrates in opposite directions across the cell membrane -Lactose permease transports lactose and protons together in the same direction U1-14 Membrane Ca2+-ATPases: Overview [Full Text] [PDF] -Intracellular calcium levels are mainly regulated by ATP-dependent calcium pumps -The sarcoplasmic reticulum Ca2+-ATPase governs the calcium content of muscle cells -The activity of Ca2+-ATPases is highly regulated U1-15 Membrane Ca2+-ATPases: SERCA Structure and Function [Full Text] [PDF] -The Ca2+-ATPase of the sarcoplasmic reticulum is the best understood ion pump -The sarcoplasmic reticulum Ca2+-ATPase is a molecular machine driven by large conformational changes Updates – 2004-2005 Back to top Secondary structure U1-1 Importance and Determinants of Secondary Structure [Full Text] [PDF] -Folded proteins have segments of regular conformation -The arrangement of secondary structure elements provides a convenient way of classifying types of folds -Steric constraints dictate the possible types of secondary structure -The simplest secondary structure element is the beta turn U1-2 Prediction of Secondary Structure [Full Text] [PDF] -Certain amino acids are more usually found in alpha helices, others in beta sheets Protein folding U1-3 Principles of Protein Folding [Full Text] [PDF] -The folded structure of a protein is determined by its primary structure -Competition between self-interactions and interactions with water drives protein folding -Computational prediction of folding is not yet reliable -Helical membrane proteins may fold by condensation of preformed secondary structure elements in the bilayer U1-4 Chaperones and Protein Folding [Full Text] [PDF] -The interior of the cell presents special obstacles to protein folding -Chaperones assist folding of newly synthesized and misfolded proteins U1-5 Protein Misfolding and Disease [Full Text] [PDF] -The cell has several strategies for coping with misfolded proteins -Depletion or accumulation of misfolded proteins can lead to many types of disease Chapter 2: From Structure to Function [PDF] Back to top 2-0 Overview: The Structural Basis of Protein Function [Full Text] [PDF] -There are many levels of protein function -There are four fundamental biochemical functions of proteins 2-1 Recognition, Complementarity and Active Sites [Full Text] [PDF] -Protein functions such as molecular recognition and catalysis depend on complementarity -Molecular recognition depends on specialized microenvironments that result from protein tertiary structure -Specialized microenvironments at binding sites contribute to catalysis 2-2 Flexibility and Protein Function [Full Text] [PDF] -The flexibility of tertiary structure allows proteins to adapt to their ligands -Protein flexibility is essential for biochemical function -The degree of flexibility varies in proteins with different functions 2-3 Location of Binding Sites [Full Text] [PDF] -Binding sites for macromolecules on a protein's surface can be concave, convex, or flat -Binding sites for small ligands are clefts, pockets or cavities -Catalytic sites often occur at domain and subunit interfaces 2-4 Nature of Binding Sites [Full Text] [PDF] -Binding sites generally have a higher than average amount of exposed hydrophobic surface -Binding sites for small molecules are usually concave and partly hydrophobic -Weak interactions can lead to an easy exchange of partners -Displacement of water also drives binding events -Contributions to binding affinity can sometimes be distinguished from contributions to binding specificity 2-5 Functional Properties of Structural Proteins [Full Text] [PDF] -Proteins as frameworks, connectors and scaffolds -Some structural proteins only form stable assemblies -Some catalytic proteins can also have a structural role -Some structural proteins serve as scaffolds 2-6 Catalysis: Overview [Full Text] [PDF] -Catalysts accelerate the rate of a chemical reaction without changing its overall equilibrium -Catalysis usually requires more than one factor -Catalysis is reducing the activation-energy barrier to a reaction 2-7 Active-Site Geometry [Full Text] [PDF] -Reactive groups in enzyme active sites are optimally positioned to interact with the substrate 2-8 Proximity and Ground-State Destabilization [Full Text] [PDF] -Some active sites chiefly promote proximity -Some active sites destabilize ground states 2-9 Stabilization of Transition States and Exclusion of Water [Full Text] [PDF] -Some active sites primarily stabilize transition states -Many active sites must protect their substrates from water, but must be accessible at the same time 2-10 Redox Reactions [Full Text] [PDF] -A relatively small number of chemical reactions account for most biological transformations -Oxidation/reduction reactions involve the transfer of electrons and often require specific cofactors 2-11 Addition/Elimination, Hydrolysis and Decarboxylation [Full Text] [PDF] -Addition reactions add atoms or chemical groups to double bonds, while elimination reactions remove them to form double bonds -Esters, amides and acetals are cleaved by reaction with water; their formation requires removal of water -Loss of carbon dioxide is a common strategy for removing a single carbon atom from a molecule 2-12 Active-Site Chemistry [Full Text] [PDF] -Active sites promote acid-base catalysis 2-13 Cofactors [Full Text] [PDF] -Many active sites use cofactors to assist catalysis 2-14 Multi-Step Reactions [Full Text] [PDF] -Some active sites employ multi-step mechanisms 2-15 Multifunctional Enzymes [Full Text] [PDF] -Some enzymes can catalyze more than one reaction -Some bifunctional enzymes have only one active site -Some bifunctional enzymes contain two active sites 2-16 Multifunctional Enzymes with Tunnels [Full Text] [PDF] -Some bifunctional enzymes shuttle unstable intermediates through a tunnel connecting the active sites -Trifunctional enzymes can shuttle intermediates over huge distances -Some enzymes also have non-enzymatic functions Updates – 2007-2008 Back to top Protein interactions – Chapter 3 on Principles and Mechanisms of Protein Interactions from Cell Signaling by Lim, Mayer and Pawson 3-0 Overview: Binding Interactions between Signaling Proteins [Full Text] [PDF] -Changes in protein binding are important for transmitting signals -Changes in protein binding have both direct and indirect functional consequences -Protein binding is regulated in many ways in the cell 3-1 Properties of Protein–Protein Interactions [Full Text] [PDF] -Protein binding can be mediated by broad interaction surfaces or by short, linear peptides -Modular protein-binding and lipid-binding domains are important in signaling -Dynamic protein assemblies that transduce signals have different properties from stable macromolecular complexes 3-2 Affinity and Specificity [Full Text] [PDF] -The affinity and specificity of an interaction determine how likely it is to occur in the cell -Specificity is determined by the relative affinities of competing interactions -The likelihood of a protein interaction in a cell depends on the cellular and molecular context 3-3 The Dissociation Constant and Binding Energy [Full Text] [PDF] -The strength of a binding interaction is defined by the dissociation constant (Kd) -The dissociation constant is related to the binding energy of the interaction 3-4 Binding Kinetics [Full Text] [PDF] -The dissociation constant is also related to rates of binding and unbinding -The apparent Kd can be strongly affected by the local cellular environment and other binding partners 3-5 Tuning of Affinities and Specificities for Biological Function [Full Text] [PDF] -Ideal affinity and specificity depends on biological function and ligand concentrations -There are functional constraints on interaction affinities and specificities 3-6 Mechanisms for Tuning Interaction Affinity and Specificity [Full Text] [PDF] -Affinity and specificity can be independently modulated -Positive discrimination can increase affinity without increasing specificity -Negative discrimination can increase specificity without increasing affinity 3-7 Cooperative Binding [Full Text] [PDF] -A variety of experimental methods are used to detect protein–protein interactions -Cooperativity involves the coupled binding of multiple ligands -Diverse molecular mechanisms underlie cooperativity -Cooperative binding has a variety of functional consequences 3-8 Mapping Protein–Protein Interactions [Full Text] [PDF] -Interacting proteins can be identified by isolating protein complexes from cell extracts -Binding partners can be identified by screening large libraries of genes -Direct protein–protein interactions can be detected by solid-phase screening 3-9 Analyzing Protein–Protein Interactions in Living Cells [Full Text] [PDF] -Interactions can be visualized and quantified in living cells -Fluorescent protein tags are used to locate and track proteins in cells -Protein–protein interactions can be visualized directly in living cells 3-10 Experimental Determination of Quantitative Binding Parameters [Full Text] [PDF] -Analytical methods can determine quantitative binding parameters -Equilibrium binding studies can be used to determine the dissociation constant -Rates of binding and dissociation, and thermodynamic binding parameters, can be determined experimentally -Binding parameters are important for quantitative modeling of signaling pathways Updates – 2005-2006 Back to top Enzyme kinetics U2-1 Enzyme Kinetics: General Principles [Full Text] [PDF] -Reaction rates reflect key properties of enzymes and the reactions they catalyze -Reaction rates depend on collisions between reacting species, which in turn depend on concentrations and temperature -Reaction kinetics are described by rate constants U2-2 Fundamental Kinetic Properties of Enzyme-Catalyzed Reactions [Full Text] [PDF] -Vmax and Km are two key measurable properties of enzymes -Enzyme-catalyzed reactions must involve formation of an enzyme–substrate complex, followed by one or more chemical steps -Enzyme kinetic parameters can be determined by several analytical methods U2-3 Analysis of Enzyme Reaction Rate Data [Full Text] [PDF] -kcat/Km can be interpreted in terms of enzyme specificity and catalytic efficiency -Enzyme-catalyzed reactions can have multiple steps with several intermediates -The temperature dependence of enzyme reactions provides information about transition state energies U2-4 Enzyme Regulation: Kinetic Consequences [Full Text] [PDF] -Enzyme reactions can be slowed by the presence of inhibitors -Enzyme reactions can be activated by the binding of extraneous ligands Chapter 3: Control of Protein Function [PDF] Back to top 3-0 Overview: Mechanisms of Regulation [Full Text] [PDF] -Protein function in living cells is precisely regulated -Proteins can be targeted to specific compartments and complexes -Protein activity can be regulated by binding of an effector and by covalent modification -Protein activity may be regulated by protein quantity and lifetime -A single protein may be subject to many regulatory influences 3-1 Protein Interaction Domains [Full Text] [PDF] -The flow of information within the cell is regulated and integrated by the combinatorial use of small protein domains that recognize specific ligands 3-2 Regulation by Location [Full Text] [PDF] -Protein function in the cell is context-dependent -There are several ways of targeting proteins in cells 3-3 Control by pH and Redox Environment [Full Text] [PDF] -Protein function is modulated by the environment in which the protein operates -Changes in redox environment can greatly affect protein structure and function -Changes in pH can drastically alter protein structure and function 3-4 Effector Ligands: Competitive Binding and Cooperativity [Full Text] [PDF] -Protein function can be controlled by effector ligands that bind competitively to ligand-binding or active sites -Cooperative binding by effector ligands amplifies their effects 3-5 Effector Ligands: Conformational Change and Allostery [Full Text] [PDF] -Effector molecules can cause conformational changes at distant sites -ATCase is an allosteric enzyme with regulatory and active sites on different subunits -Disruption of function does not necessarily mean that the active site or ligand-binding site has been disrupted -Binding of gene regulatory proteins to DNA is often controlled by ligand-induced conformational changes 3-6 Protein Switches Based on Nucleotide Hydrolysis [Full Text] [PDF] -Conformational changes driven by nucleotide binding and hydrolysis are the basis for switching and motor properties of proteins -All nucleotide switch proteins have some common structural and functional features 3-7 GTPase Switches: Small Signaling G Proteins [Full Text] [PDF] -The switching cycle of nucleotide hydrolysis and exchange in G proteins is modulated by the binding of other proteins 3-8 GTPase Switches: Signal Relay by Heterotrimeric GTPases [Full Text] [PDF] -Heterotrimeric G proteins relay and amplify extracellular signals from a receptor to an intracellular signaling pathway 3-9 GTPase Switches: Protein Synthesis [Full Text] [PDF] -EF-Tu is activated by binding to the ribosome, which thereby signals it to release its bound tRNA 3-10 Motor Protein Switches [Full Text] [PDF] -Myosin and kinesin are ATP-dependent nucleotide switches that move along actin filaments and microtubules respectively 3-11 Regulation by Degradation [Full Text] [PDF] -Protein function can be controlled by protein lifetime -Proteins are targeted to proteasomes for degradation 3-12 Control of Protein Function by Phosphorylation [Full Text] [PDF] -Protein function can be controlled by covalent modification -Phosphorylation is the most important covalent switch mechanism for the control of protein function 3-13 Regulation of Signaling Protein Kinases: Activation Mechanism [Full Text] [PDF] -Protein kinases are themselves controlled by phosphorylation -Src kinases both activate and inhibit themselves 3-14 Regulation of Signaling Protein Kinases: Cdk Activation [Full Text] [PDF] -Cyclin acts as an effector ligand for cyclin-dependent kinases 3-15 Two-Component Signaling Systems in Bacteria [Full Text] [PDF] -Two-component signal carriers employ a small conformational change that is driven by covalent attachment of a phosphate group 3-16 Control by Proteolysis: Activation of Precursors [Full Text] [PDF] -Limited proteolysis can activate enzymes -Polypeptide hormones are produced by limited proteolysis 3-17 Protein Splicing: Autoproteolysis by Inteins [Full Text] [PDF] -Some proteins contain self-excising inteins -The mechanism of autocatalysis is similar for inteins from unicellular organisms and metazoan Hedgehog protein 3-18 Glycosylation [Full Text] [PDF] -Glycosylation can change the properties of a protein and provide recognition sites 3-19 Protein Targeting by Lipid Modifications [Full Text] [PDF] -Covalent attachment of lipids targets proteins to membranes and other proteins -The GTPases that direct intracellular membrane traffic are reversibly associated with internal membranes of the cell 3-20 Methylation, N-acetylation, Sumoylation and Nitrosylation [Full Text] [PDF] -Fundamental biological processes can also be regulated by other post-translational modifications of proteins Updates – 2007-2008 Back to top Protein phosphatases U3-3 Protein Phosphatases: Structure and Catalytic Mechanisms [Full Text] [PDF] -Protein phosphatases fall into several groups -Protein serine/threonine phosphatases are metalloproteins -Protein tyrosine phosphatases function via a phosphoenzyme intermediate and include receptors as well as cytoplasmic enzymes -Some phosphoinositide phosphatases are related to protein tyrosine phosphatases U3-4 Protein Phosphatases: Pathways and Regulation [Full Text] [PDF] -Phosphatases function in conjunction with protein kinases to regulate signaling Updates – 2004-2005 Back to top Control by pH and redox U3-1 Control by pH [Full Text] [PDF] -Protein function is modulated by the pH of the environment in which the protein operates -Changes in pH can drastically alter protein structure and function U3-2 Redox Control [Full Text] [PDF] -Changes in redox environment can greatly affect protein structure and function -Cells have specific mechanisms to control their internal redox environment -Redox-dependent protein modifications can regulate biological activity Chapter 4: From Sequence to Function [PDF] Back to top 4-0 Overview: From Sequence to Function in the Age of Genomics [Full Text] [PDF] -Genomics is making an increasing contribution to the study of protein structure and function 4-1 Sequence Alignment and Comparison [Full Text] [PDF] -Sequence comparison provides a measure of the relationship between genes -Alignment is the first step in determining whether two sequences are similar to each other -Multiple alignments and phylogenetic trees 4-2 Protein Profiling [Full Text] [PDF] -Structural data can help sequence comparison find related proteins -Sequence and structural motifs and patterns can identify proteins with similar biochemical functions -Protein-family profiles can be generated from multiple alignments of protein families for which representative structures are known 4-3 Deriving Function from Sequence [Full Text] [PDF] -Sequence information is increasing exponentially -In some cases function can be inferred from sequence 4-4 Experimental Tools for Probing Protein Function [Full Text] [PDF] -Gene function can sometimes be established experimentally without information from protein structure or sequence homology 4-5 Divergent and Convergent Evolution [Full Text] [PDF] -Evolution has produced a relatively limited number of protein folds and catalytic mechanisms -Proteins that differ in sequence and structure may have converged to similar active sites, catalytic mechanisms and biochemical function -Proteins with low sequence similarity but very similar overall structure and active sites are likely to be homologous -Convergent and divergent evolution are sometimes difficult to distinguish -Divergent evolution can produce proteins with sequence and structural similarity but different functions 4-6 Structure from Sequence: Homology Modeling [Full Text] [PDF] -Structure can be derived from sequence by reference to known protein folds and protein structures -Homology modeling is used to deduce the structure of a sequence with reference to the structure of a close homolog 4-7 Structure from Sequence: Profile-Based Threading and "Rosetta" [Full Text] [PDF] -Profile-based threading tries to predict the structure of a sequence even if no sequence homologs are known -The Rosetta method attempts to predict protein structure from sequence without the aid of a homologous sequence or structure 4-8 Deducing Function from Structure: Protein Superfamilies [Full Text] [PDF] -Members of a structural superfamily often have related biochemical functions -The four superfamilies of serine proteases are examples of convergent evolution -Very closely related protein families can have completely different biochemical and biological functions 4-9 Strategies for Identifying Binding Sites [Full Text] [PDF] -Binding sites can sometimes be located in three-dimensional structures by purely computational means -Experimental means of locating binding sites are at present more accurate than computational methods 4-10 Strategies for Identifying Catalytic Residues [Full Text] [PDF] -Site-directed mutagenesis can identify residues involved in binding or catalysis -Active-site residues in a structure can sometimes be recognized computationally by their geometry -Docking programs model the binding of ligands 4-11 TIM Barrels: One Structure with Diverse Functions [Full Text] [PDF] -Knowledge of a protein's structure does not necessarily make it possible to predict its biochemical or cellular functions 4-12 PLP Enzymes: Diverse Structures with One Function [Full Text] [PDF] -A protein's biochemical function and catalytic mechanism do not necessarily predict its three-dimensional structure 4-13 Moonlighting: Proteins with More than One Function [Full Text] [PDF] -In multicellular organisms, multifunctional proteins help expand the number of protein functions that can be derived from relatively small genomes 4-14 Chameleon Sequences: One Sequence with More than One Fold [Full Text] [PDF] -Some amino-acid sequences can assume different secondary structures in different structural contexts 4-15 Prions, Amyloids and Serpins: Metastable Protein Folds [Full Text] [PDF] -A single sequence can adopt more than one stable structure 4-16 Functions for Uncharacterized Genes: Galactonate Dehydratase [Full Text] [PDF] -Determining biochemical function from sequence and structure becomes more accurate as more family members are identified -Alignments based on conservation of residues that carry out the same active-site chemistry can identify more family members than sequence comparisons alone -In well studied model organisms, information from genetics and cell biology can help identify the substrate of an "unknown" enzyme and the actual reaction catalyzed 4-17 Starting from Scratch: A Gene Product of Unknown Function [Full Text] [PDF] -Function cannot always be determined from sequence, even with the aid of structural information and chemical intuition Chapter 5: Structure Determination [PDF] Back to top 5-1 The Interpretation of Structural Information [Full Text] [PDF] -Experimentally determined protein structures are the result of the interpretation of different types of data -Both the accuracy and the precision of a structure can vary -The information content of a structure is determined by its resolution 5-2 Structure Determination by X-Ray Crystallography and NMR [Full Text] [PDF] -Protein crystallography involves summing the scattered X-ray waves from a macromolecular crystal -NMR spectroscopy involves determining internuclear distances by measuring perturbations between assigned resonances from atoms in the protein in solution 5-3 Quality and Representation of Crystal and NMR Structures [Full Text] [PDF] -The quality of a finished structure depends largely on the amount of data collected -Different conventions for representing the structures of proteins are useful for different purposes Updated References [Full Text] [PDF]  | ||||||||||||||||||||||||||||||||||||||||||||||||||||
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