The history of molecular biology began in the 1930s with the convergence of various previously different biological and physical disciplines: biochemistry, genetics, microbiology, virology and physics. In the hope of understanding life at the most fundamental level, many physicists and chemists are also interested in what would become molecular biology.
In its modern sense, molecular biology tries to explain the phenomenon of life from the nature of the macromolecules that produce it. Two categories of macromolecules in particular are the focus of molecular biologists: 1) nucleic acids, among which the most famous are deoxyribonucleic acid (or DNA), gene constituents, and 2) proteins, which are active agents of living organisms.. One definition of the scope of molecular biology is therefore to characterize the structures, functions and relationships between these two types of macromolecules. This relatively limited definition would be sufficient to allow us to set a date for the so-called "molecular revolution", or at least to build the chronology of its most basic development.
Video History of molecular biology
Overview
In its earliest manifestations, molecular biology - the name invented by Warren Weaver of the Rockefeller Foundation in 1938 - is the notion of physical and chemical explanation of life, rather than coherent discipline. Following the emergence of Mendelian-chromosome heredity theory in the 1910s and the maturation of atomic theory and quantum mechanics in the 1920s, such explanations seem within reach. Weaver and others encourage (and fund) research at the intersection of biology, chemistry and physics, while prominent physicists such as Niels Bohr and Erwin SchrÃÆ'¶dinger turn their attention to biological speculation. However, in the 1930s and 1940s it was by no means clear - if anything - cross-disciplinary research would bear fruit; working in the fields of colloid chemistry, biophysics and radiation biology, crystallography, and other emerging fields all seem promising.
In 1940, George Beadle and Edward Tatum showed an exact relationship between genes and proteins. In their experiments linking genetics with biochemistry, they shifted from Drosophila's primetical genetics to more precise model organisms, fungi Neurospores ; the construction and exploitation of new model organisms will be the themes that often appear in the development of molecular biology. In 1944, Oswald Avery, who worked at Rockefeller Institute of New York, pointed out that genes consist of DNA (see Avery-MacLeod-McCarty experiment). In 1952, Alfred Hershey and Martha Chase confirmed that the genetic material of bacteriophage, a virus that infects bacteria, consists of DNA (see Hershey-Chase experiment). In 1953, James Watson and Francis Crick discovered the double helical structure of the DNA molecule. In 1961, FranÃÆ'§ois Jacob and Jacques Monod showed that certain gene products regulate the expression of other genes by acting on a particular site on the edge of the gene. They also hypothesize the existence of an intermediary between DNA and its protein products, which they call messenger RNA. Between 1961 and 1965, the relationship between information contained in DNA and protein structure was determined: there was a code, a genetic code, which created a correspondence between nucleotide succession in DNA sequences and a series of amino acids in proteins.
The major discovery of molecular biology occurs in a period of only about twenty-five years. It will take fifteen more years before new and more sophisticated technologies, now united under the name of genetic engineering, will allow the isolation and characterization of genes, especially very complex organisms.
Maps History of molecular biology
Exploration of molecular power
If we evaluate the molecular revolution in the context of biological history, it is easy to note that it is the culmination of a long process that begins with the first observation through a microscope. The purpose of these early researchers was to understand the functioning of living organisms by describing their organizations on a microscopic level. From the late 18th century, the characterization of chemical molecules that make up living beings gained increasing attention, along with the birth of 19th century physiological chemistry, developed by German chemist Justus von Liebig and following the birth of biochemistry at the beginning of the 20th, thanks to chemists Another German, Eduard Buchner. Between molecules studied by chemists and small structures seen under optical microscopes, such as cell nuclei or chromosomes, there is an obscure zone, the "neglected dimensional world," as Wolfgang called chemistry-physicists. Ostwald. The world is inhabited by colloids, chemical compounds whose structures and properties are not well-defined.
The success of molecular biology comes from the exploration of the unknown world through new technology developed by chemists and physicists: X-ray diffraction, electron microscopy, ultracentrifugation, and electrophoresis. These studies reveal the structure and function of macromolecules.
A milestone in the process is Dr. Linus Pauling and Dr. Eze Benjamin O in 1949, for the first time linking specific genetic mutations in patients with sickle cell disease to changes shown in individual proteins, hemoglobin in individual heterozygous or homozygous erythrocytes.
Meeting between biochemistry and genetics
The development of molecular biology is also a meeting of two disciplines that made great progress in the first thirty years of the 20th century: biochemistry and genetics. The first studied the structure and function of the molecules that make up living things. Between 1900 and 1940, the main processes of metabolism are described: the process of digestion and the absorption of nutrients derived from alimentation, such as sugar. Each of these processes is catalyzed by certain enzymes. Enzymes are proteins, such as antibodies present in the blood or proteins responsible for muscle contraction. As a result, the study of their proteins, their structures and their synthesis, became one of the biochemistry's major objectives.
The second biological discipline developed in the early 20th century was genetics. After the rediscovery of Mendel's laws through the study of Hugo de Vries, Carl Correns and Erich von Tschermak in 1900, this science began to be formed thanks to the adoption by Thomas Hunt Morgan, in 1910, from model organisms to genetic studies. , the famous fruit fly ( Drosophila melanogaster ). Shortly after, Morgan pointed out that the gene is localized to the chromosome. Following this discovery, he continues to work with Drosophila and, along with many other research groups, underscores the importance of genes in the life and development of organisms. However, the gene's chemical properties and their mechanism of action remain a mystery. Molecular biologists are committed to the determination of structures, and the description of the intricate relationships between, genes and proteins.
The development of molecular biology is not only the fruit of a kind of intrinsic "need" in the history of ideas, but is a distinctive historical phenomenon, with all the unknown, unpredictable and contingent: the remarkable developments in physics at the beginning of the 20th Century highlight the relative delays in the development of biology, which became the "new boundary" in the search for knowledge of the empirical world. Moreover, the development of information theory and cybernetics in the 1940s, in response to military urgency, brought to new biology a large number of fertile ideas and, in particular, metaphors.
The choice of bacteria and viruses, bacteriophages, as models for studying the basic mechanisms of life are almost natural - they are the smallest living organisms known to exist - and at the same time the fruit of individual choice. This model owes its success, above all, to the fame and sense of the organization of Max DelbrÃÆ'¼ck, a German physicist, who is able to create a dynamic research group based in the United States, whose exclusive sphere is the study of bacteriophages:/i>.
The geographic panorama of new biological developments is conditioned above all by previous work. The United States, where genetics is developing most rapidly, and Britain, where there is good coexistence of both genetic and biochemical research, is at the forefront. Germany, the birthplace of the revolution in physics, with the best minds and the most sophisticated genetic laboratories in the world, should have a major role in the development of molecular biology. But history decides differently: the arrival of the Nazis in 1933 - and, to a lesser extent, its fascist totalitarian size in fascist Italy - led to the emigration of large numbers of Jewish and non-Jewish scientists. The majority of them fled to the US or the UK, giving an extra boost to the scientific dynamics of these countries. These movements eventually make molecular biology a truly international science from the very beginning.
The history of DNA biochemistry
The study of DNA is a core part of molecular biology.
First DNA isolation
Working in the 19th century, biochemists initially isolated DNA and RNA (mingled together) from the cell nucleus. They were relatively quick to appreciate the polymeric properties of their "nucleic acid" isolates, but only later realized that nucleotides consist of two types - one containing ribose and other deoxyribose. The next discovery is what causes the identification and naming of DNA as a different substance from RNA.
Friedrich Miescher (1844-1895) discovered a substance which he called "nuclein" in 1869. Some time later, he isolated a pure sample of material now known as DNA from salmon sperm, and in 1889 his disciple Richard Altmann named it " nucleus ". This substance is found only on chromosomes.
In 1919, Phoebus Levene at the Rockefeller Institute identified components (four bases, sugars and phosphate chains) and he showed that the DNA components were related in the phosphate-sugar-base sequence. He referred to each of these units as nucleotides and suggested a DNA molecule consisting of a series of nucleotide units connected together via a phosphate group, which is the 'backbone' of the molecule. However Levene thought the chain was short and that the bases repeated in the same order. TorbjÃÆ'¶rn Caspersson and Einar Hammersten show that DNA is a polymer.
Chromosomes and inherited properties
In 1927 Nikolai Koltsov proposed that inherited traits would be inherited through a "gigantic molecule" which would consist of "two mirrored strands that would replicate in a semi-conservative way using each strand as a template". Max DelbrÃÆ'¼ck, Nikolay Timofeev-Ressovsky, and Karl G. Zimmer published the results in 1935 showing that chromosomes are very large molecules whose structures can be altered by X-ray treatment, and that by altering their structure it is possible to alter inherited characteristics governed by the chromosome. In 1937 William Astbury produced the first X-ray diffraction pattern of DNA. He can not propose the correct structure but the pattern shows that DNA has a regular structure and therefore it is possible to infer what this structure is.
In 1943, Oswald Theodore Avery and his team of scientists discovered that the exact properties for the "delicate" shape of Pneumococcus could be transferred to a "rough" form of the same bacteria simply by making the killed ones. "smooth" (S) shapes are available for rough "live" (R) forms. Quite unexpectedly, the living bacteria R Pneumococcus is transformed into a new strain of the S form, and the transferred S character is inherited. Avery calls the transfer medium the characteristics of the transformation principle; it identifies DNA as the principle of transformation, and not the protein as previously thought. He basically changed Frederick Griffith's experiments. In 1953, Alfred Hershey and Martha Chase conducted experiments (Hershey-Chase experiments) which showed, in the T2 freak, that DNA was a genetic material (Hershey shared the Nobel Prize with Luria).
Discovery of DNA structure
In the 1950s, three groups made it their goal to define the structure of DNA. The first group to start was at King's College London and led by Maurice Wilkins and later joined Rosalind Franklin and Eze Benjamin O. Another group consisting of Francis Crick and James Watson was in Cambridge. The third group is at Caltech and led by Linus Pauling. Crick and Watson construct a physical model using metal rods and balls, where they incorporate known chemical structures of nucleotides, as well as known positions of the connections that connect one nucleotide to the next along the polymer. At King's College, Maurice Wilkins and Rosalind Franklin examined the X-ray diffraction patterns of the DNA fibers. Of the three groups, only the London group was able to produce a good quality diffraction pattern and thus produce sufficient quantitative data about the structure.
Helix Structure
In 1948 Pauling discovered that many proteins included helical forms (see alpha helix). Pauling has deduced this structure from the X-ray pattern and from attempting to model the structure physically. (Pauling also suggests one of the wrong DNA structures of the helix chain based on Astbury data.) Even in the early DNA diffraction data by Maurice Wilkins, it is clear that the structure involves a helix. But this insight is only the beginning. There are still questions about how many unified strands, whether this number is the same for each helix, whether the base points toward the axis of the helix or away, and finally what is the angle and explicit coordinates of all bonds and atoms. Such questions motivated Watson and Crick modeling efforts.
Complementary nucleotides
In their modeling, Watson and Crick limit themselves to what they consider chemically and biologically reasonable. However, the extent of the possibility is very broad. A breakthrough occurred in 1952, when Erwin Chargaff visited Cambridge and inspired Crick with a description of the experiment that Chargaff had published in 1947. Chargaff has observed that the proportion of four nucleotides varies between one DNA sample and the next, but for certain couples of nucleotides - adenine and thymine, guanine and cytosine - two nucleotides are always present in equal proportions.
By using X-ray diffraction, as well as other data from Rosalind Franklin and the information that the base is paired, James Watson and Francis Crick arrived at the first accurate model of DNA molecule structure in 1953, received through an examination by Rosalind Franklin. The discovery was announced on 28 February 1953; the first Watson/Crick paper appeared in Nature on April 25, 1953. Sir Lawrence Bragg, director of the Cavendish Laboratory, where Watson and Crick worked, gave a talk at Guy's Hospital Medical School in London on Thursday, May 14, 1953 produced an article by Ritchie Calder in London's News Chronicle, on Friday, May 15, 1953, entitled "Why You Are You The Secret of A Closer Life." The news reached the reader of The New York Times the next day; Victor K. McElheny, in researching his biography, "Watson and DNA: Making a Scientific Revolution", invented the clippings of a six-paragraph article New York Times written from London and dated May 16, 1953 under the title "Form of` Life Unit 'in Cell Is Scanned. "The article was published in the initial edition and then withdrawn to make room for more important news. ( The New York Times subsequently published a longer article on June 12, 1953). The Cambridge University scholar's paper also published his own short article on the discovery on Saturday, May 30, 1953. Bragg's original announcement at the Solvay Conference on protein in Belgium on April 8, 1953 was not reported by the press. In 1962 Watson, Crick, and Maurice Wilkins jointly received the Nobel Prize in Physiology or Medicine for the determination of the structure of DNA.
"Central Dogma"
The Watson and Crick models drew great interest immediately after the presentation. Arriving at their conclusion on February 21, 1953, Watson and Crick made their first announcement on February 28th. In an influential presentation in 1957, Crick placed the "central dogma of molecular biology", which predicted the relationship between DNA, RNA, and proteins, and articulated "sequential hypotheses." Critical confirmation of the replication mechanism implied by the double helix structure followed in 1958 in the Meselson-Stahl experiment. Work by Crick and colleagues shows that the genetic code is based on an overlapping triplet of the base, called codon, and Har Gobind Khorana and the others deciphering the genetic code shortly thereafter (1966). These findings represent the birth of molecular biology.
History of tertiary RNA structures
Pre-history: RNA helical structure
The earliest work in structural biology of RNA coincided, more or less, with work done on DNA in the early 1950s. In their 1953 seminal paper Watson and Crick stated that the van der Waals crowd by the 2'OH riboso group would prevent RNA from adopting a double helical structure identical to the model they proposed - now known as B-form DNA. This provokes the question of the three-dimensional structure of RNA: can these molecules form several types of helical structures, and if so, how? Like DNA, early structural work on RNA centered around the original RNA polymer insulation for fiber diffraction analysis. Partly because of the heterogeneity of the samples tested, the initial fiber diffraction patterns are usually ambiguous and not easily interpreted. In 1955, Marianne Grunberg-Manago and colleagues published a paper describing the enzyme polynukleotide phosphorylase, which divides the phosphate group of the diphosphate nucleotides to catalyze their polymerization. This discovery allows researchers to synthesize homogeneous nucleotide polymers, which are then combined to produce double-stranded molecules. These samples yield the easiest interpreted fiber diffraction patterns that have not yet been obtained, showing a regular helical structure for rations, double-stranded RNAs that are different from those observed in DNA. These results pave the way for a series of investigations into the various traits and trends of RNA. Through the late 1950s and early 1960s, numerous papers were published on various topics in RNA structures, including RNA-DNA hybridization, three-stranded RNAs, and even small-scale crystallographic RNA di-nucleotides - GC, and AU - in primitive helices - like settings. For a more in-depth look at the initial work in RNA structural biology, see the article RNA Awakening Era: RNA structural biology in the early years by Alexander Rich.
Beginning: crystal structure of tRNA PHE
In the mid-1960s, the role of tRNAs in protein synthesis was being studied intensively. At this point, ribosomes have been implicated in protein synthesis, and it has been shown that mRNA strands are required for the formation of this structure. In the 1964 publication Warner and Rich showed that the ribosomes active in protein synthesis contain tRNA molecules bound to sites A and P, and discuss the idea that these molecules are helpful in peptidyl transferase reactions. However, despite considerable biochemical characterization, the structural basis of the tRNA function remains a mystery. In 1965, Holley et al. purifies and sequences the first tRNA molecule, initially proposing that it adopt the clover leaf structure, based largely on the ability of certain regions of the molecule to form a parent loop structure. Isolation of tRNA proved to be the first major fortune in RNA structural biology. After the publication of Robert W. Holley, many researchers began working on isolation tRNAs for crystallographic studies, developing improved methods to isolate molecules as they worked. By 1968 some groups had produced tRNA crystals, but this proved to have limited quality and did not produce data at the resolution required to define the structure. In 1971, Kim et al. reached another breakthrough, producing a yeast tRNA PHE crystal which diffracted to 2-3 ÃÆ'... lactation resolution using spermine, which occurs naturally. polyamines, which bind and stabilize tRNAs. Despite having a suitable crystal, the PHE tRNA structure is not immediately resolved at high resolution; instead of needing pioneering work in the use of heavy metal derivatives and more time to produce high density maps of all molecules. In 1973, Kim et al. produces a 4 ng map ÃÆ'... of a tRNA molecule in which they can clearly track the entire spine. This solution will be followed by many more, as various researchers work to improve the structure and thereby more thoroughly explain the details of the base pair and the interaction of the stack, and validate the published architecture of the molecule.
The structure of the famous PHE tRNA structure is well known in the area of ​​nucleic acid structure in general, as it represents the first solution of any long chain nucleic acid structure of any type - RNA or DNA - before Richard E. Dickerson B-shape dodecamer solution by nearly one decades. Also, the PHE tRNA shows many of the tertiary interactions observed in an RNA architecture that will not be categorized and better understood comprehensively for years to come, providing the foundation for all future RNA structural research.
The renaissance: my hammer ribozymes and group intron: P 4-6
For a long time following the structure of the first tRNA, the field of RNA structure did not increase dramatically. The ability to study RNA structures depends on the potential to isolate RNA targets. This has proven to be limiting to the field for years, partly because other known targets - ie, ribosomes - are significantly more difficult to isolate and crystallize. Furthermore, since other interesting RNA targets have not been identified, or are sufficiently understood to be considered attractive, there are few things to be studied structurally. Thus, for about twenty years after the original publication of the PHE tRNA structure, the structure of only a handful of other RNA targets was resolved, with almost all family-owned RNA diversions. This lack of scope will ultimately be overcome mainly due to two major advances in nucleic acid research: the identification of ribozymes, and the ability to produce them via in vitro transcription .
Following the publication of Tom Cech involving the Tetrahymena group I intron as an autocatalytic ribozyme, and Sidney Altman's report on catalysis by RNA P ribonuclease, several other catalytic RNAs were identified in the late 1980s, including hammerhead ribozymes. In 1994, McKay et al. publishes the structure of a hammerhead RNA-DNA ribozyme-inhibitor complex at a resolution of 2.6 ÃÆ'... ngstrÃÆ'¶m, in which the autocatalytic activity of the ribozyme is disrupted through binding. to the DNA substrate. The conformation of the ribozyme published in this paper eventually proves to be one of several possible circumstances, and although this particular sample is catalytically inactive, subsequent structures have revealed the architecture of its active state. This structure was followed by Jennifer Doudna's publication of the P4-P6 domain structure of the tetrahymena group I am intron, a fragment of ribozyme originally made famous by Cech. The second clause in the title of this publication - Packing RNA Principle - briefly describes the value of these two structures: for the first time, comparisons can be made between well-defined tRNA structures and globular RNAs. outside the transfer family. This allows the categorization framework to be built for tertiary RNA structures. It is now possible to propose conservation of motives, folds, and local stabilization interactions. For a preliminary review of this structure and its implications, see FASE RNA: Insights from the latest crystal structure , by Doudna and Ferre-D'Amare.
In addition to the advances made in the determination of global structures through crystallography, the early 1990s also saw the application of NMR as a powerful technique in RNA structural biology. Coinciding with large scale crystallographic ribozyme structures, a number of small RNA structures and RNA complexed with drugs and peptides were completed using NMR. In addition, NMR is now being used to investigate and supplement crystal structures, as exemplified by the isolation of isolated tetraloop receptor motif structures published in 1997. Such investigations allow for more precise characterization of base pairs and basic stacking interactions that stabilize the global fold of molecules Great RNA. The importance of understanding the structural motif of tertiary tertiary RNA prophetically described by Michel and Costa in their publication identifies the tetraloop motif: "... it should not be surprising that self-RNA molecules are used intensively only with relatively small size tertiary set patterns. this will greatly help modeling companies, which will remain important as long as large RNA crystallization remains a difficult task ".
The modern era: the age of structural biology RNA
The rise of structural biology of RNA in the mid-1990s has led to a noticeable explosion in the field of structural research of nucleic acids. Since the publication of the hammerhead structure and P 4-6 , many of the major contributions to this field have been made. Some of the most important examples include the inton structure of Groups I and Group II, and Ribosome solved by Nenad Ban and colleagues at Thomas Steitz's laboratory. It should be noted that the first three structures were produced using in vitro transcription , and that NMR has played a role in investigating the partial components of the four testimonial structures with the need for both techniques for RNA research. More recently, the 2009 Nobel Prize in Chemistry has been awarded to Ada Yonath, Venkatraman Ramakrishnan and Thomas Steitz for their structural work on the ribosome, showing the prominent role that has been taken by RNA structural biology in modern molecular biology.
History of protein biochemistry
First isolation and classification
Proteins are recognized as distinct classes of biological molecules in the eighteenth century by Antoine Fourcroy and others. Members of this class (called "albuminoids", "EiweisskÃÆ'¶rper", or matiÃÆ'¨res albuminoides ) are recognized by their ability to thicken or flocculate under various treatments such as heat or acid; notable examples of the early nineteenth century included albumen of egg whites, blood serum albumin, fibrin, and wheat gluten. The similarity between cooking egg whites and thickening milk is recognized even in ancient times; for example, the name albumen for the egg white protein was created by Pliny the Elder from Latin albus ovi (egg white).
With advice from JÃÆ'¶ns Jakob Berzelius, Dutch chemist Gerhardus Johannes Mulder analyzed the animal protein elements and common plants. To everyone's surprise, all proteins have almost the same empirical formulas, about C 400 H 620 N 100 O 120 with individual sulfur and phosphorus atoms. Mulder published his findings in two papers (1837,1838) and hypothesized that there was one substance ( Grundstoff ) protein, and that it was synthesized by plants and absorbed from them by animals in the digestion. Berzelius was an early proponent of this theory and proposed the name "protein" for this substance in a letter dated July 10, 1838.
The name protein that he proposes for organic oxide fibrin and albumin, I want to take from [Greek word] ????????, because it seems it is the primitive element or the principal of animal nutrition.
Mulder went on to identify protein degradation products such as amino acids, leucine, where he found the molecular weight (almost correct) of 131 Da.
Purification and mass measurement
The minimum molecular weight suggested by the Mulder analysis is approximately 9 kDa, hundreds of times larger than any other molecule being studied. Therefore, the chemical structure of the protein (their main structure) was an active area of ​​research until 1949, when Fred Sanger sequenced insulin. The (correct) theory that proteins are linear polymers of amino acids linked by peptide bonds is proposed independently and simultaneously by Franz Hofmeister and Emil Fischer at the same conference in 1902. However, some scientists are skeptical that such long macromolecules can be stable in solution.. Consequently, many alternative theories of the proposed primary structure of the protein, for example, the colloid hypothesis that proteins are small molecular assemblies, the cyclot hypothesis Dorothy Wrinch, hypothesis diketopiperazine Emil Abderhalden and pyrrol/piperidine hypothesis from Troensgard (1942). Most of these theories have difficulty in accounting for the fact that protein digestion produces peptides and amino acids. The protein finally proved to be a well-defined macromolecule composition (and not a colloidal mixture) by Theodor Svedberg using ultracentrifugation analytics. The possibility that some proteins are non-covalent associations of such macromolecules is indicated by Gilbert Smithson Adair (by measuring the osmotic pressure of hemoglobin) and, later, by Frederic M. Richards in his study of ribonuclease S. Mass protein spectrometry has long been a useful technique for identifying post-transformation modification and, more recently, to examine protein structure.
Most proteins are difficult to purify in quantities more than milligrams, even using the most modern methods. Therefore, preliminary studies focus on proteins that can be purified in large quantities, for example, blood, egg white, various toxins, and digestive/metabolic enzymes obtained from slaughterhouses. Many protein purification techniques were developed during World War II in a project led by Edwin Joseph Cohn to purify blood proteins to help keep the army alive. In the late 1950s, Armor Hot Dog Co. purify 1 kg (= one million milligrams) of pure bovine pancreatic A ribonuclease and make it available for free to scientists around the world. This generous act makes RNase A the main protein for basic research over the next few decades, producing several Nobel Prizes.
Protein fold and first structure model
The study of protein folding began in 1910 with well-known papers by Harriette Chick and CJ Martin, where they showed that protein flocculation consists of two distinct processes: the precipitation of a protein from a solution preceded by another process called denaturation, in where the protein becomes much less soluble, loses its enzymatic activity and becomes more chemically reactive. In the mid-1920s, Tim Anson and Alfred Mirsky proposed that denaturation is an invertible process, a true hypothesis that was originally criticized by some scientists as "flipping through eggs". Anson also suggested that denaturation is a two-state process ("all-or-none"), in which a fundamental molecular transition produces a drastic change in solubility, enzymatic activity and chemical reactivity; he further notes that the free energy changes when denaturation is much smaller than those normally involved in chemical reactions. In 1929, Hsien Wu hypothesized that denaturation is a stretched protein, a purely conformational change that results in the exposure of amino acid side chains to the solvent. According to this (correct) hypothesis, the exposure of the aliphatic and reactive side chains to the solvent makes the protein less soluble and more reactive, whereas the loss of certain conformations results in the loss of enzymatic activity. Although considered reasonable, Wu's hypothesis is not immediately accepted, since so little is known about the structure of proteins and enzymes and other factors can explain changes in solubility, enzymatic activity and chemical reactivity. In the early 1960s, Chris Anfinsen showed that the fold of ribonuclease A is completely reversible without the necessary external cofactors, verifying the "folding thermodynamic hypothesis" of fold proteins that folded states represent the global minimum of free energy for proteins.
The fold protein hypothesis is followed by research into the physical interactions that stabilize the folded protein structure. An important role of hydrophobic interaction is hypothesized by Dorothy Wrinch and Irving Langmuir, as a mechanism that may stabilize the cyclone structure. Although supported by J. D. Bernal and others, this correct hypothesis was rejected along with the cyclot hypothesis, which was not proven in 1930 by Linus Pauling (among others). Instead, Pauling championed the idea that the structure of proteins is stabilized primarily by hydrogen bonds, an idea advanced initially by William Astbury (1933). Remarkably, Pauling's false theory of the H-bond yields a true model for the secondary structural elements of proteins, alpha helix and beta sheets. Hydrophobic interactions were restored to true fame by a famous article in 1959 by Walter Kauzmann on denaturation, partly based on work by Kaj LinderstrÃÆ'¸m-Lang. The ionic properties of proteins are shown by Bjerrum, Weber and Arne Tiselius, but Linderstrom-Lang suggests that the allegations are generally accessible to solvents and not tied to one another (1949).
The secondary and low-resolution structures of globular proteins were investigated initially by hydrodynamic methods, such as analytical ultracentrifugation and birefringence flow. Spectroscopic methods for investigating protein structure (such as circular dichroism, fluorescence, almost ultraviolet and infrared absorbance) were developed in the 1950s. The first atomic-resolution structure of the protein was solved by X-ray crystallography in the 1960s and by NMR in the 1980s. In 2006, Protein Data Bank has nearly 40,000 atomic resolution protein structures. In more recent times, cryo-electron microscopy of large macromolecular assemblies and the prediction of small protein computational protein domain structures are two methods that are close to atomic resolution.
See also
- Biological history
- Biotechnology history
- Genetic history
References
Source
Source of the article : Wikipedia
0 Comments