Keywords:
Proteins.
;
Electronic books.
Type of Medium:
Online Resource
Pages:
1 online resource (482 pages)
Edition:
1st ed.
ISBN:
9781136665493
URL:
https://ebookcentral.proquest.com/lib/geomar/detail.action?docID=5992771
DDC:
572/.636
Language:
English
Note:
Intro -- COPYRIGHT PAGE -- PREFACE -- CONTENTS -- DETAILED CONTENTS -- Chapter 1 Protein Structure and Evolution -- 1.1 Structures of amino acids and peptides -- 1.1.1 Proteins are composed of amino acids -- 1.1.2 Amino acids have only a few allowed conformations -- 1.1.3 The most populated conformation is in the beta-sheet region -- 1.1.4 The other main conformations are the alpha helix and the "random coil" -- 1.1.5 The pK[sub]a[/sub] value describes the protonation behavior of side chains -- 1.2 The forces holding proteins together -- 1.2.1 Electrostatic forces can be strong -- 1.2.2 Hydrogen bonds are formed by electrostatic dipoles -- 1.2.3 Van der Waals forces are individually weak but collectively strong -- 1.2.4 The hydrophobic interaction is entropic in origin -- 1.2.5 Hydrogen bonds are uniquely directional -- 1.2.6 Cooperativity is a feature of large systems -- 1.2.7 The formation of a beta hairpin is cooperative -- 1.2.8 Hydrogen bond networks are cooperative -- 1.2.9 Proteins require a layer of water for their function -- 1.2.10 Entropy and enthalpy tend to change in compensatory directions -- 1.3 The structure of proteins -- 1.3.1 Proteins are composed of primary, secondary, tertiary, and quaternary structure -- 1.3.2 Secondary structures pack together in structure motifs -- 1.3.3 Membrane proteins are different from globular proteins -- 1.3.4 The structure of a protein is (more or less) determined by its sequence -- 1.3.5 Some proteins form metastable structures -- 1.3.6 Structure is conserved more than sequence -- 1.3.7 Structural homology can be used to identify function -- 1.4 The evolution of proteins -- 1.4.1 What are the purposes of proteins? -- 1.4.2 Evolution is a tinker -- 1.4.3 Many proteins arose by gene duplication -- 1.4.4 Most new proteins arise by modification of duplicated genes.
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1.4.5 Evolutionary tinkering leaves its fingerprints behind -- 1.4.6 New proteins can arise by gene sharing -- 1.4.7 Evolution usually retains chemistry and alters binding -- 1.4.8 Convergent and divergent evolution are difficult to distinguish -- 1.4.9 New functions may often develop from promiscuous or moonlighting precursors -- 1.4.10 Retrograde evolution is not common -- 1.4.11 Proteins began in an RNA world -- 1.4.12 Most evolutionary innovation happened very early -- 1.5 Summary -- 1.6 Further reading -- 1.7 Websites -- Some molecular graphics programs -- 1.8 Problems -- 1.9 Numerical problems -- 1.10 References -- Chapter 2 Protein Domains -- 2.1 Domains: the fundamental unit of protein structure -- 2.1.1 Domains can be defined in a variety of ways -- 2.1.2 Domains can usually be associated with specific functions -- 2.1.3 Domains are the basic building blocks of proteins -- 2.1.4 Modules are transposable domains -- 2.2 The key role of domains in protein -- 2.2.1 Multidomain proteins are produced by exon shuffling -- 2.2.2 Multidomain proteins are also produced by other genetic mechanisms -- 2.2.3 Evolution can proceed in jumps by three-dimensional domain swapping -- 2.2.4 Three-dimensional domain swapping still occurs -- 2.2.5 Increased binding specificity is conferred by additional domain interactions -- 2.2.6 Intramolecular binding is strong because the effective concentration is high -- 2.2.7 Intramolecular interactions lead to cooperative hydrogen bonding -- 2.2.8 Intramolecular domain:peptide binding facilitates autoinhibition -- 2.2.9 Intramolecular domain:peptide binding facilitates evolutionary change -- 2.2.10 Binding specificity is increased by scaffold proteins -- 2.2.11 Intramolecular binding is strong because it has less unfavorable entropy -- 2.3 Potential advantages of multidomain construction.
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2.3.1 Multidomain construction makes it simple to evolve a new function -- 2.3.2 Multidomain construction makes it simple to introduce control and regulation -- 2.3.3 Multidomain construction makes an effective enzyme -- 2.3.4 Multidomain construction simplifies folding and assembly and stabilizes the protein -- 2.4 Proteins as tools -- 2.4.1 Tools have independently moving parts -- 2.4.2 Tools have a common design but different sizes -- 2.4.3 Tools have common parts with variable "ends" -- 2.4.4 Some tools are symmetric -- 2.4.5 Some tools have a specialist use -- 2.5 Summary -- 2.6 Further reading -- 2.7 Websites -- 2.8 Problems -- 2.9 Numerical problems -- 2.10 References -- Chapter 3 Oligomers -- 3.1 Why do proteins oligomerize? -- 3.1.1 Oligomerization shelters and regulates the active site -- 3.1.2 Oligomerization provides improved enzyme functionality -- 3.1.3 Oligomerization makes symmetric dimers -- 3.1.4 Coding errors, coding efficiency and linkers are not convincing reasons -- 3.2 Allostery -- 3.2.1 Most enzymes are not allosteric -- 3.2.2 Hemoglobin is the classic example of allostery -- 3.2.3 Oxygen affinity in hemoglobin is fine-tuned by other effectors -- 3.2.4 There are two main models for allostery -- 3.2.5 Glycogen phosphorylase is another good example of allostery -- 3.3 Cooperative binding of dimers to DNA -- 3.3.1 Cooperativity can be understood by using thermodynamics -- 3.3.2 Sequence-specific binding to DNA is a problem -- 3.3.3 The trp repressor recognizes DNA by hinge bending -- 3.3.4 CAP recognizes DNA by rotation around the dimer interface -- 3.3.5 DNA recognition by a symmetric leucine zipper -- 3.3.6 DNA recognition by a heterodimeric leucine zipper -- 3.3.7 Max and Myc form a heterodimeric zipper with alternative partners -- 3.3.8 DNA recognition by a tandem dimer -- 3.4 Isozymes -- 3.5 Summary -- 3.6 Further reading.
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3.7 Websites -- 3.8 Problems -- 3.9 Numerical problems -- 3.10 References -- Chapter 4 Protein Interactions in vivo -- 4.1 Factors influencing collision rates -- 4.1.1 On a small scale, random processes have much more significant effects -- 4.1.2 Diffusion occurs by a random walk -- 4.1.3 The collision rate is limited by geometrical factors -- 4.1.4 Collision rates can be increased by electrostatic attraction -- 4.1.5 Collision rates are also increased by electrostatic steering -- 4.1.6 Protein binding takes place via an encounter complex -- 4.1.7 Electrostatic repulsion is also important for limiting interactions -- 4.1.8 Macromolecular crowding increases the amount of protein association but slows its rate -- 4.1.9 Larger proteins diffuse more slowly -- 4.2 How proteins can find their partners faster -- 4.2.1 Processivity decreases the off-rate from polymeric substrates -- 4.2.2 Searching is much faster in two dimensions -- 4.2.3 Searching is slightly faster again in one dimension -- 4.2.4 Searching is faster in smaller compartments -- 4.2.5 Sticky arms are useful for short-range searching -- 4.2.6 Proline-rich sequences make good sticky arms -- 4.2.7 Sticky-arm interactions have fast on- and off-rates -- 4.2.8 Sticky arms are fast because they zip up rather than lock on -- 4.3 Natively unstructured proteins -- 4.3.1 Natively unstructured proteins are common -- 4.3.2 Natively unstructured proteins permit specific binding with fast on-rate -- 4.3.3 Natively unstructured proteins provide specific binding without strong binding -- 4.3.4 Natively unstructured proteins may provide other benefits -- 4.4 Post-translational modification of proteins -- 4.4.1 Covalent modifications modify protein function -- 4.4.2 Phosphorylation -- 4.4.3 Methylation and acetylation -- 4.4.4 Glycosylation -- 4.5 Protein folding and misfolding.
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4.5.1 Protein folding is often rapid and thermodynamically controlled -- 4.5.2 All proteins have a limited lifespan, especially unfolded ones -- 4.5.3 Amyloid is a consequence of protein misfolding -- 4.6 Summary -- 4.7 Further reading -- 4.8 Websites -- 4.9 Problems -- 4.10 Numerical problems -- 4.11 References -- Chapter 5 How Enzymes Work -- 5.1 Enzymes lower the energy of the transition state -- 5.1.1 What is the transition state? -- 5.1.2 Enzymes lower both enthalpy and entropy barriers in the transition state -- 5.1.3 Catalytic antibodies demonstrate the strong entropic contribution -- 5.2 Chemical catalysis -- 5.2.1 Chemical reactions involve movement of electrons -- 5.2.2 A good leaving group is important -- 5.2.3 General acid and general base catalysis are ubiquitous -- 5.2.4 Electrophilic catalysis is also common -- 5.2.5 Thermolysin uses all these mechanisms -- 5.2.6 Nucleophilic catalysis implies a change in mechanism -- 5.2.7 Enzymes often use cofactors and coenzymes -- 5.2.8 Enzymes control water in the active site -- 5.3 Enzymes recognize the transition state, not the substrate -- 5.3.1 The lock and key and induced-fit models -- 5.3.2 An enzyme should not bind strongly to its substrate -- 5.3.3 Binding and catalytic rate are closely interrelated -- 5.3.4 Transition-state analogs make good enzyme inhibitors -- 5.4 Triosephosphate isomerase -- 5.4.1 Triosephosphate isomerase uses many catalytic mechanisms -- 5.4.2 Triosephosphate isomerase is an evolutionarily perfect enzyme -- 5.5 Summary -- 5.6 Further reading -- 5.7 Problems -- 5.8 Numerical problems -- 5.9 References -- Chapter 6 Protein Flexibility and Dynamics -- 6.1 Timescales and distance scales of motions -- 6.1.1 Rapid motions are local and uncorrelated -- 6.1.2 Local motions produce global disorder.
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6.1.3 Larger-scale motions are more correlated and are therefore slower.
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