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BK

Third edition

Oxford : Oxford University Press, [2016]

xxii, 466 stran : barevné ilustrace ; 27 cm

ISBN 978-0-19-871684-6 (brožováno)

Obsahuje rejstřík

Terminologický slovník

001460467

CONTENTS // Preface to the first edition xvii // Preface to the second edition xx // Preface to the third edition xxi // 1 Introduction 1 // Proteins in their biological context 2 // The amino acids 4 // Dogmas—central and peripheral 5 // The relationship between amino acid sequence and // protein structure is robust 6 // Disorder in proteins 7 // Regulation 10 // The genetic code 11 // With life so dependent on proteins, there is ample opportunity for things to go wrong 12 // Genome sequences 15 // Gene sequence determines amino acid sequence 16 // Protein synthesis: the ribosome is the point of contact between genes and proteins—it is the fulcrum of genomics 17 // Ribosomes were implicated in protein synthesis very early on 18 // Structural studies of ribosomes by X-ray crystallography and electron microscopy 18 // Protein stability, denaturation, aggregation, and turnover 19 // Protein turnover 19 // Description of protein structures 20 // Primary structure 21 // Secondary structure: helices and sheets are favourable conformations of the chain that recur in many proteins 21 // Tertiary and quaternary structure 23 // Folding patterns in native proteins—themes and variations 23 // Modular proteins, and ’mixing and matching’ as a mechanism of evolution 25 // How do proteins develop new functions? 27 // The study of proteins: in the laboratory, in the cell, in the computer 29 // Spectroscopic methods of characterizing proteins in solution 30 // Absorbance and fluorescence

of proteins 32 // Fluorescence is sensitive to the environment and dynamics of the chromophore 34 // Fluorescence resonance energy transfer (FRET) 34 // Circular dichroisrr 34 // Protein expression patterns in space and time: proteomics 35 // Subcellular localization 35 // The transcriptome 36 // Contents // DNA microarrays 37 // Mass spectrometry 3g // Computing in protein science 38 // Computer-instrument partnerships in the laboratory 33 // Simulations, including molecular dynamics 39 // Bioinformatics 40 // Introduction to databanks for protein science 40 // Information-retrieval tools 4-] // Web access to the scientific literature 41 // Useful websites 42 // Recommended reading 42 // Exercises and Problems 43 // 2 Protein structure 46 // Introduction 47 // Structures of the amino acids 47 // Protein conformation 50 // Conformational angles and the // Sasisekharan-Ramakrishnan-Ramachandran plot 51 // Sidechain conformation 53 // Rotamer libraries 53 // Stabilization of the native state 54 // Conformational change 59 // Protein folding patterns 60 // Supersecondary structures 60 // An album of small structures 62 // Comparison of the folding patterns of acylphosphatase and a fungal toxin 64 // Classification of protein structures 67 // Databanks of protein structure classifications 68 // SCOP 68 // SCOP2 70 // CATH 71 // The DALI Database 72 // A survey of protein structures and functions 73 // Fibrous proteins 73 // Enzymes—proteins that catalyse chemical reactions 76

Antibodies 77 // Inhibitors 77 // Carrier proteins 77 // Membrane proteins 78 // Receptors 80 // Regulatory proteins 81 // Motor proteins 81 // Contents // ? // Control of protein activity 81 // Regulation of tyrosine hydroxylase illustrates several control mechanisms common to many proteins 84 // Control cascades 84 // Recommended reading 85 // Exercises and Problems 85 // 3 Protein structure determination 92 // Introduction 93 // X-ray crystallography 94 // X-ray structure determination 95 // X-ray crystallography of proteins 96 // Interpretation of the electron density: model building and improvement 100 // The endgame—refinement 102 // How accurate are the structures? 102 // X-ray crystallography—the theoretical background 104 // Nuclear magnetic resonance spectroscopy in structural biology 110 // NMR spectra of proteins 111 // Measurement of NMR spectra 113 // Protein structure determination by NMR 113 // Assignment of the spectrum 114 // Transverse relaxation optimized spectroscopy 117 // From the data to the structure 117 // Solid-state NMR: magic angle spinning 118 // Near atomic-resolution low-temperature electron microscopy (cryo-EM) 119 // Octameric pyruvate-ferredoxin oxidoreductase from Desulfovibrio vulgaris Hildenborough 120 // Conformational change in activation of human integrin aVß3 120 // Trajectories of conformational change 124 // The elastic network model accounts for conformational change in Mycobacterium tuberculosis thioredoxin reductase 125 // The

relationship between structure determinations of isolated proteins, and protein structure and function in vivo 127 // Protein structure prediction and modelling 127 // A priori methods of protein structure prediction 128 // Empirical, or ’knowledge-based’, methods of protein structure prediction 129 // Secondary structure prediction 131 // Homology modelling 133 // Fold recognition 135 // Antibody modeling 137 // Prediction of special categories of structures 139 // Conformational energy calculations and molecular dynamics 140 // ROSETTA 142 // e // Contents // Protein structure prediction from contact maps derived from correlated mutations in multiple sequence alignments 144 // Critical Assessment of Structure Prediction (CASP) 146 // CAPRI 153 // Recommended reading 153 // Exercises and Problems 154 // 4 Bioinformatics of protein sequence and structure 160 // Introduction 160 // Databases and information retrieval 161 // Amino acid sequence databases 162 // Protein databases at the U.S. National Center for Biotechnology Information 163 // Specialized, or ’boutique’, databases 164 // Nucleic acid sequence databases 165 // Genome databases and genome browsers 166 // Ensembl 166 // Expression and proteomics databases 166 // Databases of macromolecular structure 168 // Organization of wwPDB entries 169 // Retrieval of sequences and structures 170 // Retrieval of amino acid sequences by keyword 171 // The Protein Information Resource (PIR) and associated databases 171 // Retrieval

of structures by keyword 172 // Probing databanks with sequence information 173 // Sequence alignment 174 // The dotplot 175 // Dotplots and alignments 176 // BLAST and PSI-BLAST 177 // Significance of alignments 179 // Multiple sequence alignment 181 // A multiple sequence alignment of thioredoxins shows the importance of conservation patterns 182 // Analysis of structures 184 // Superposition of structures 184 // Structural alignment 185 // Multiple structure alignment 187 // Database searching for structures or fragments 187 // Databases of protein families 188 // Classifications of protein structures 189 // Classification and assignment of protein function 189 // Contents // ? // The Enzyme Commission 189 // The Gene Ontology’™ Consortium protein function classification 190 // The ENZYME database and PROSITE 192 // Databases of metabolic networks 193 // Recommended reading 194 // Exercises and Problems 195 // 5 Proteins as catalysts: enzyme structure, // kinetics, and mechanism 197 // Introduction 197 // What are the crucial features of enzymes? 198 // Reaction rates and transition states 201 // The activated complex 203 // Measurement of reaction rates 204 // Slow the reaction down 205 // Fast methods of data collection 205 // Active sites 206 // Cofactors 206 // Protein-ligand binding equilibria 207 // The Scatchard plot 207 // Catalysis by enzymes 208 // Enzyme kinetics 209 // Derivation of KM and Vmax from rate data 210 // Measures of effectiveness of enzymes 211

Inhibitors 212 // Irreversible inhibitor binding 212 // Multisubstrate reactions 213 // Enzyme mechanisms 214 // The mechanism or action of thymidylate synthase 216 // Computational approaches to enzyme mechanisms 218 // The mechanism of action of chymotrypsin 220 // The evidence from kinetics 221 // The evidence from crystallography 221 // Blood coagulation 222 // Thrombosis 222 // Serpins: serine proteinase inhibitors-conformational disease 226 // Several conformational states of serpins are known 227 // Mechanism of proteinase inhibition by serpins 228 // Evolutionary divergence of enzymes 229 // The mechanism of action of malate and lactate dehydrogenases 229 // Contents // Enolase, mandelate racemase, and muconate lactonizing enzyme catalyse different reactions but have related mechanisms 230 // The structure and mechanism of E. coli topoisomerase III 231 // Motor proteins 233 // The sliding filament mechanism of muscle contraction 233 // ATP synthase 234 // Membrane transport 238 // Specificity of the potassium channel from Streptomyces lividans—room to swing a cation? 238 // Allosteric regulation of protein activity 239 // The allosteric structural change of haemoglobin 242 // Recommended reading 246 // Exercises and Problems 246 // 6 Proteins with partners 252 // Introduction 252 // General properties of protein-protein interfaces 254 // Burial of protein surface 254 // The composition of the interface 254 // Complementarity 254 // Specific interactions at protein-protein

interfaces 255 // Phage M13 gene III protein and E. coli TolA 255 // Multisubunit proteins 256 // Diseases of protein aggregation 257 // Amyloidoses 258 // Alzheimer’s disease 258 // Prion diseases—spongiform encephalopathies 259 // The immune system 260 // Antibody structure 261 // Antibody maturation 266 // Catalytic antibodies—’abzymes’ 267 // Proteins of the major histocompatibility complex 268 // T-cell receptors 273 // Virus structures 274 // Tomato bushy stunt virus 278 // Bacteriophage HK97: protein chain-mail 278 // Photosynthetic reaction centres 279 // Protein-DNA interactions 280 // Structural themes in protein-DNA binding and sequence recognition 281 // Bacteriophage T7 DNA polymerase 282 // Some protein-DNA complexes that regulate gene transcription 283 // Recommended reading 287 // Exercises and Problems 288 // Contents // 7 Evolution of protein structure and function 291 // Introduction 291 // Protein structure classification 294 // A case study: superpositions and alignments of pairs of proteins with // increasingly more-distant relationships 296 // Structural relationships among homologous domains 298 // Changes in proteins during evolution give clues to the roles of residues at different positions 302 // To what constraints are pathways of protein evolution subject? 302 // Closed /3-barrel structures 303 // The TIM barrel 303 // Evolution of the globins 307 // Mammalian globins 308 // What determines the globin folding pattern? 310 // Truncated globins 312

// Expansion of the globin family 313 // Classification of the globins 313 // Globin functions 316 // Phycocyanins and the globins 316 // Evolution of NAD-binding domains of dehydrogenases 318 // Comparison of NAD-binding domains of dehydrogenases 320 // The sequence motif G*G**G 323 // Structure and evolution of serine proteinases of the chymotrypsin family 324 // Structures of individual domains 324 // The domain/domain interface 326 // The specificity pocket 327 // The /3-barrels in serine proteinase domains and the packing of residues in their interiors 328 // Evolution of visual pigments and related molecules 331 // Selection has tuned vertebrate opsins so that the absorption maximum varies with the light environment 335 // How do proteins evolve new functions? 338 // Pathways and limits in the divergence of sequence, structure and function 339 // Evolution of functional change in the enolase superfamily 342 // Protein evolution at the level of domain assembly 345 // Domain swapping is a general mechanism for forming an oligomer from a multidomain protein 345 // Directed evolution 346 // Directed evolution of subtilisin E 347 // Enhancement of thermal stability 347 // Activity in organic solvents 348 // Affinity selectivity by phage display 349 // Recommended reading 350 // Exercises and Problems 350 // Contents // 8 Protein folding and design 356 // Introduction 356 // Why is protein folding so fast? 357 // Thermodynamics—key concepts 358 // Entropy 359 // Spontaneity

and equilibrium 359 // Kinetics ?60 // Thermodynamics of protein folding 360 // Thermodynamics of mutated proteins 361 // Experimental characterization of events in protein folding 362 // The molten globule ?63 // Folding funnels ?64 // The effect of denaturants on rates of folding and unfolding: chevron plots 365 // The kinetics of folding of mutated proteins gives clues to the structure of the transition state for folding 365 // Comparison of folding pathways of a natural protein and a circular permutant 366 // Relationship between native structure and folding 369 // The hierarchical model of protein folding 371 // How fast could a protein fold? 372 // Protein misfolding and the GroEL-GroES chaperone protein 373 // The GroEL-GroES conformational change 375 // Protein engineering 376 // Protein design 376 // ab initio design of a hyperstable variant of Streptococcal protein G, /31 domain 376 // Expanding and contracting the genetic code 378 // Expansion of the genetic code 378 // Contraction of the genetic code 381 // Understanding the contents and layout of the common genetic code 382 // Recommended reading 382 // Exercises and Problems 383 // 9 Proteomics and systems biology 387 // Introduction 388 // Separation and analysis of proteins 389 // Polyacrylamide gel electrophoresis 389 // Two-dimensional polyacrylamide gel electrophoresis 390 // Difference gel electrophoresis 390 // Contents // Mass spectrometry // Identification of components of a complex mixture Protein sequencing

by mass spectrometry Quantitative analysis of relative abundance Measuring deuterium exchange in proteins // ’Ome, ‘ome, on the range—environmental genomics and proteomics // Metagenomics // Metaproteomics // Dynamic proteomics of the response to cadmium challenge // Microarrays // Microarray data are semiquantitative Applications of DNA microarrays // Analysis of microarray data // Expression patterns in different physiological states Expression pattern changes in development: the life cycle of Drosophila melanogaster // RNAseq // RNAseq v. microarrays // Systems biology // Two parallel networks: physical and logical Networks and graphs // Robustness and redundancy Connectivity in networks Dynamics, stability, and robustness // Protein complexes and aggregates Protein interaction networks // Regulatory networks // Structures of regulatory networks Structural biology of regulatory networks // Gene regulation // The transcriptional regulatory network of E. coli Regulation of the lactose operon in E. coli // The genetic regulatory network of Saccharomyces cerevisiae // Adaptability of the yeast regulatory network // Recommended reading // Exercises and Problems