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Showing papers in "Proceedings of the National Academy of Sciences of the United States of America in 1951"


Journal ArticleDOI
TL;DR: This work has used information about interatomic distances, bond angles, and other configurational parameters to construct two reasonable hydrogen-bonded helical configurations for the polypeptide chain; it is likely that these configurations constitute an important part of the structure of both fibrous and globular proteins, as well as of syntheticpolypeptides.
Abstract: During the past fifteen years we have been attacking the problem of the structure of proteins in several ways. One of these ways is the complete and accurate determination of the crystal structure of amino acids, peptides, and other simple substances related to proteins, in order that information about interatomic distances, bond angles, and other configurational parameters might be obtained that would permit the reliable prediction of reasonable configurations for the polypeptide chain. We have now used this information to construct two reasonable hydrogen-bonded helical configurations for the polypeptide chain; we think that it is likely that these configurations constitute an important part of the structure of both fibrous and globular proteins, as well as of synthetic polypeptides. A letter announcing their discovery was published last year [1]. The problem that we have set ourselves is that of finding all hydrogen-bonded structures for a single polypeptide chain, in which the residues are equivalent (except for the differences in the side chain R). An amino acid residue (other than glycine) has no symmetry elements. The general operation of conversion of one residue of a single chain into a second residue equivalent to the first is accordingly a rotation about an axis accompanied by translation along the axis. Hence the only configurations for a chain compatible with our postulate of equivalence of the residues are helical configurations. For rotational angle 180° the helical configurations may degenerate to a simple chain with all of the principal atoms, C, C' (the carbonyl carbon), N, and O, in the same plane.

2,506 citations


Journal ArticleDOI
TL;DR: In recent papers, several configurations of polypeptide chains with interatomic distances, bond angles, and other structural features as indicated by the studies in these Laboratories of the structure of crystals of amino acids, simple peptides, and related substances are described.
Abstract: In recent papers we have described several configurations of polypeptide chains with interatomic distances, bond angles, and other structural features as indicated by the studies in these Laboratories of the structure of crystals of amino acids, simple peptides, and related substances, and have presented evidence for their presence in synthetic polypeptides, fibrous proteins, and globular proteins.(1-9)

749 citations


Journal ArticleDOI
TL;DR: These notes are a preliminary account of a general theory of Green’s functions, in which the defining property is taken to be the representation of the fields of prescribed sources.
Abstract: The temporal development of quantized fields, in its particle aspect, is described by propagation functions, or Green’s functions. The construction of these functions for coupled fields is usually considered from the viewpoint of perturbation theory. Although the latter may be resorted to for detailed calculations, it is desirable to avoid founding the formal theory of the Green’s functions on the restricted basis provided by the assumption of expandability in powers of coupling constants. These notes are a preliminary account of a general theory of Green’s functions, in which the defining property is taken to be the representation of the fields of prescribed sources.

741 citations



Journal ArticleDOI
TL;DR: It is shown that in silk fibroin, stretched hair and muscle, and other proteins with the β-keratin structure the polypeptide chains are extended to nearly their maximum length, and that a hydrogen-bonded layer of this sort is represented diagrammatically in figure 1.
Abstract: For many years it has been assumed that in silk fibroin, stretched hair and muscle, and other proteins with the β-keratin structure the polypeptide chains are extended to nearly their maximum length, about 3.6 A per residue, and during the last decade it has been assumed also that the chains form lateral hydrogen bonds with adjacent chains, which have the opposite orientation. A hydrogen-bonded layer of this sort is represented diagrammatically in figure 1.(1-4)

551 citations




Journal ArticleDOI
TL;DR: The discovery of two helical configurations of the polypeptide chain that satisfy the conditions for diffraction of x-rays in the equatorial direction are reported.
Abstract: During recent years we have been gathering information about interatomic distances, bond angles, and other properties of simple substances related to proteins, and have been attempting to formulate configurations of the polypeptide chain that are compatible with this information and that might constitute a structural feature of proteins. We have reported the discovery of two helical configurations that satisfy these conditions. (1,2) In the following paragraphs we discuss the atomic positions for these configurations, and their form factors for diffraction of x-rays in the equatorial direction.

364 citations




Journal ArticleDOI
TL;DR: Attempts were made to confer insolubility on protein antigens such as ovalbumin and crystalline bovine serum albumin without destroying their antigenicity, but in every case the resulting product had lost too much native antigenicity or had too much power of adsorption for non-specific protein.
Abstract: For the past several years we have been interested in devising methods that would afford practical procedures for the isolation and purification of antibodies from immune serums and in particular the isolation of non-precipitating antibodies from animal serums and allergic antibodies (reagins) from human serums.(1) The general approach has been to attempt to produce an insoluble protein antigen which would combine specifically with antibody to give a complex that could be dissociated into soluble antibody and insoluble antigen, which could then be separated by centrifugation. Attempts were made to confer insolubility on protein antigens such as ovalbumin and crystalline bovine serum albumin without destroying their antigenicity. Products were obtained by use of the usual denaturing agents, tannic acid, and bifunctional coupling reagents (e.g., tetrazotized benzidine), and also by coupling to an insoluble substrate such as phenolic resins or insoluble proteins (such as fibrin). However, in every case the resulting product either had lost too much native antigenicity (i.e., adsorbed serum always contained antibody which reacted with native antigen), was too soluble, or had too much power of adsorption for non-specific protein.

Journal ArticleDOI
TL;DR: Evidence that one of the helical structures is assumed also by synthetic polypeptides is discussed, which is an important structural feature of hemoglobin and other globular proteins.
Abstract: In a preliminary communication last year(1) we stated that there are only two helical configurations of polypeptide chains in which the residues are all equivalent and intramolecular hydrogen bonds are formed, and in which the interatomic distances, bond angles, and other structural features, especially the coplanarity of the conjugated amide system, are as required by earlier work in these Laboratories on amino acids, simple peptides, and other substances related to protein's. These two helical configurations were described in detail in a later paper(2) and it was mentioned that there is evidence that they occur in α keratin, α myosin, supercontracted keratin and myosin, and other fibrous proteins, and also constitute an important structural feature of hemoglobin and other globular proteins.(3) In the following paragraphs we discuss evidence that one of the helical structures is assumed also by synthetic polypeptides.

Journal ArticleDOI
TL;DR: Electron microscope studies have demonstrated that the reconstituted fibril reconstitution from acid filtrates of collagen show the axial period and intraperiod fine structure typical of native collagen fibrils although the acid Filtrate contains only very thin filaments.
Abstract: The collagen of certain forms of connective tissue, such as rat tail tendon and the fish swin bladder (ichthyocol), dissolve in dilute acid to yield a clear, relatively viscous solution. When NaCl is added to such a solution to a concentration of 0.2-1.0%, or if the solution be neutralized, a fibrous precipitate of collagen is produced.l-3 Electron microscope studies have demonstrated that the reconstituted fibrils show the axial period and intraperiod fine structure typical of native collagen fibrils although the acid filtrate contains only very thin filaments.4 5 The process by which the thin filaments in the acid filtrate aggregate laterally to produce the typical collagen structure is of interest not only from the physical chemical point of view but also because a better understanding of the phenomenon may provide clues as to the mechanism of fibrogenesis in vivo. Investigations of the process of fibril reconstitution from acid filtrates of collagen by the

Journal ArticleDOI
TL;DR: A series of data are presented which demonstrate the applicability of simple chromatographic methods to the problems of investigating biochemical changes which occur during development of Drosophila melanogaster and studying biochemical differences between mutants of this organism.
Abstract: The principal aim of the present report is to present a series of data which demonstrate the applicability of simple chromatographic methods to the problems of investigating biochemical changes which occur during development of Drosophila melanogaster and studying biochemical differences between mutants of this organism. Extensive analyses of the data and their significance in relation to the work of other investigators will be reserved, for the most part, for subsequent and more detailed presentations.

Journal ArticleDOI
TL;DR: A number of investigators have attempted to find the structure of collagen (and of gelatin, which gives similar x-ray photographs), but no one has previously proposed any precisely described configuration, nor has attempted to account for the positions and intensities of the x-rays diffraction maxima.
Abstract: Collagen is a very interesting protein. It has well-defined mechanical properties (great strength, reversible extensibility through only a small range) that make it suited to the special purposes to which it is put in the animal body, as in tendon, bone, tusk, skin, the cornea of the eye, intestinal tissue, and probably rather extensively in reticular structures of cells. During the last thirty years, following the pioneer work of Herzog and Jancke,(1) a number of investigators have attempted to find the structure of collagen (and of gelatin, which gives similar x-ray photographs), but no one has previously proposed any precisely described configuration, nor has attempted to account for the positions and intensities of the x-ray diffraction maxima.

Journal ArticleDOI
TL;DR: The present report deals with the identification of still another form of human hemoglobin in five members of a family in which the genetic picture is not typical of sickle cell anemia, although two of the members have in the past been diagnosed as having sicklecell anemia.
Abstract: Previous work from these Laboratories has established the existence of an abnormal hemoglobin in sickle cell trait and sickle cell anemia and has provided the basis for a theory relating the presence of the abnormal hemoglobin to the clinical pictures in sickle cell trait and sickle cell anemia [1]. It was shown in this work that the electrophoretic picture in these conditions is compatible with the usual genetic picture that both parents of an individual suffering from sickle cell anemia have the sickle cell trait [2]. There are in the literature, however, a number of reports in which one of the parents of a sickle cell anemia victim possesses non-sickling erythrocytes. In some cases of this type the parent whose cells do not sickle has been shown to have thalassemia minor (Cooley's trait), and hematologic studies on the erythrocytes of the anemic individual have revealed the presence of properties which are present in the erythrocytes both of sickle cell disease and of thalassemia [3,4]. In other cases the hemoglobin of the parent having the non-sickling cells has a greater electrophoretic mobility on the acid side of the isoelectric point than either normal hemoglobin or sickle cell hemoglobin, and the hemoglobin of the anemic child contains both this new hemoglobin and sickle cell hemoglobin [5]. The present report deals with the identification of still another form of human hemoglobin in five members of a family in which the genetic picture is not typical of sickle cell anemia, although two of the members have in the past been diagnosed as having sickle cell anemia. An earlier study of this family disclosed that the two anemic children and the father, who was not anemic, had sickling erythrocytes while the mother, two sisters and two brothers of the anemic children had non-sickling erythrocytes and were not anemic [6]. The father, one brother and one sister were not available for the present study.


Journal ArticleDOI
TL;DR: In this paper, the problem of describing the nature of the generating functions of a 2-way infinite matrix with non-negative minors has been studied and its solution has been partially solved.
Abstract: A real matrix, finite or infinite, is called totally positive if and only if all its minors, of all orders = 1, 2,..., are non-negative. An infinite sequence $$ {a_0},{a_1},{a_2}, \ldots ,\quad \left( {{a_0} = 1} \right), $$ is said to be totally positive(2) if and only if the 2-way infinite matrix Open image in new window is totally positive, i. e. has only non-negative minors. We are concerned with the problem of describing the nature of the generating functions $$f\left( z \right) = a_0 + a_1 z + a_2 z^2 + \ldots$$ (2) of totally positive sequences. The problem will be partially solved in the present note and its solution will be completed in the immediately following note by Albert Edrei.


Journal ArticleDOI
TL;DR: The experiments reported in this paper concern the mechanisms involved in plant respiration, particularly those involved in the oxidation of pyruvate, and the interest of such a study lies in the fact that it has not heretofore been possible to bring about the further oxidation in vitro by any enzyme system of plant origin.
Abstract: The experiments reported in this paper concern the mechanisms involved in plant respiration, particularly those involved in the oxidation of pyruvate. The interest of such a study lies in the fact that although pyruvate is well established as an intermediate in the respiratory oxidation of hexose by plant tissues,(1) it has not heretofore been possible to bring about the further oxidation of pyruvate in vitro by any enzyme system of plant origin.


Journal ArticleDOI
TL;DR: In this article, the authors proposed structures for hair, muscle, and related proteins in the extended state (β keratin and β myosin) and the contracted state (α keratin and αmyosin), and discussed the extent to which diffraction data are accounted for by the proposed structures.
Abstract: It is thirty years since x-ray photographs were first made of hair, muscle, nerve, and sinew, by Herzog and Jancke.(1) During this period, despite the efforts of many investigators, the photographs have eluded detailed interpretation, and the molecular structures of the proteins have remained undetermined. In the present paper we propose structures for hair, muscle, and related proteins in the extended state (β keratin and β myosin) and the contracted state (α keratin and α myosin), and discuss the extent to which the diffraction data are accounted for by the proposed structures.

Journal ArticleDOI
TL;DR: To validate conclusions drawn from visual examination of spectrograms, or, more generally, to determine the stimulus correlates of perceived speech, it will often be necessary to make controlled modifications in the spectrogram, and then to evaluate the effects of those modifications on the sound as heard.
Abstract: of contexts, an investigator can arrive at a description of the acoustic features common to all of the samples, and in this way make progress toward defining the so-called invariants of speech, that is, the essential information-bearing sound elements on which the listener's identifications critically depend. The investigator can also take account of the variations among spectrograms, and by correlating these with the observed variations in pronunciation, he can begin to sort out the several acoustic features in relation to the several aspects of the perception. There are, however, many questions about the relation between acoustic stimulus and auditory perception which cannot be answered merely by an inspection of spectrograms, no matter how numerous and varied these may be. For any given unit characteristic of the auditory perception, such as the simple identification of a phoneme, the spectrogram will very often exhibit several features which are distinctive to the eye, and the information which can be obtained from the spectrogram is, accordingly, ambiguous. Even when only one feature or pattern is strikingly evident, one cannot be certain about its auditory significance, unless he assumes that those aspects of the spectrogram which appear most prominently on visual examination are, in fact, of greatest importance to the ear. That assumption, as we shall try to point out later in this paper, is itself extremely interesting, but it has not been directly tested, nor, indeed, has it always been made fully explicit. To validate conclusions drawn from visual examination of spectrograms, or, more generally, to determine the stimulus correlates of perceived speech, it will often be necessary to make controlled modifications in the spectrogram, and then to evaluate the effects of those modifications on the sound as heard. For these purposes, we have constructed an instrument, called


Journal ArticleDOI
TL;DR: The raw result of experience may be expressed by the relation A = B, B = C, A < C which may be regarded as the formula for the physical continuum, according to Poincare.
Abstract: Poincare repeatedly emphasized that only in the mathematical continuum the equalities A = B and B = C imply the equality A = C. In the observable physical continuum, “equal” means “indistinguishable,” and A = B and B = C by no means imply A = C. “The raw result of experience may be expressed by the relation \(A = B, B = C, A < C\) which may be regarded as the formula for the physical continuum.” According to Poincare, physical equality is a non-transitive relation.