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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The members of the rabbit and human beta-like globin gene families have been compared both by a computer-generated dot matrix graphical analysis of each entire gene and by calculating divergences in the coding regions. The rabbit-human gene pairs beta 4-epsilon, beta 3-gamma, psi beta 2-delta, and beta 1-beta were identified as orthologous on the basis of sequence similarities found in flanking and intervening sequences as well as by quantitative divergence calculations. The orthologous genes are in the same order on the chromosome in each species, which suggests that an ancestral family with the arrangement 5'-epsilon-gamma-delta-beta-3' preceded the mammalian radiation. Descendants of ancestral epsilon have diverged more slowly than other beta-like genes and are expressed only in embryonic life. Descendants of ancestral gamma and beta diverged at a higher rate and are expressed at wider range of developmental times. Descendants of delta have undergone nonreciprocal recombination at a high frequency and are often pseudogenes. Paralogous comparisons among the rabbit beta-like globin genes show that the beta 4-beta 3 and psi beta 2-beta 1 pairs are most similar and that beta 4 and beta 3 are more closely related to beta 1 than to psi beta 2. This fits with a branching pattern where the primordial beta split into ancestral epsilon/gamma and delta/beta genes, which later split into epsilon and gamma or delta and beta, respectively. Rabbit genes beta 4 and beta 1 acquired similar 3' untranslated regions after the epsilon/gamma split but prior to the mammalian radiation, presumably via a gene conversion event. The 5' end of beta 2 apparently converted with beta 1 after the radiation, and afterward it became a pseudogene.
Mol Biol Evol 1984 Sep
PMID:Comparison of the beta-like globin gene families of rabbits and humans indicates that the gene cluster 5'-epsilon-gamma-delta-beta-3' predates the mammalian radiation. 659 73

Analysis of the tertiary structural alterations in hemoglobin induced by ligand binding demonstrates that an allosteric core composed of the heme, histidine F8, the FG corner and part of the F-helix plays an essential role in co-operativity. This conclusion is based on structural and spectroscopic data and theoretical studies of hemoglobin chains. The methodology employed in the calculations is presented with details of the empirical energy function. Energy minimized structures of the unliganded hemoglobin chains, which serve as reference systems for the analysis, are described. To determine the structural changes induced by ligand binding, the effects of Fe--N bond shortening and of heme translation and tilting perturbations are examined. Energy minimization in the presence of the perturbations serves to provide information concerning the globin structural modifications produced by them. The validity of the results is supported by comparisons with the X-ray data of Anderson, Pulsinelli, Baldwin and Chothia on tertiary changes in the hemoglobin subunits. Internal to the allosteric core, there appear to be two stable positions for its elements: one of these corresponds to the liganded and the other to the unliganded species. The unliganded geometry fits without strain into the deoxy tetramer, while the liganded one fits without strain into the oxy tetramer. On ligation of a subunit in the deoxy tetramer, the structural changes within the allosteric core are in the direction of those found in going from the unliganded deoxy to the liganded oxy system, although they are reduced by the presence of constraints due to the other subunits in the deoxy tetramer. In addition, the quaternary constraints in the deoxy tetramer prevent the large overall displacement of the allosteric core that occurs in the transition to the liganded oxy tetramer. The coupling between the changes internal to the allosteric core, produced on ligation and the overall displacement of the core that accompanies the quaternary transition, is an essential element of the co-operative mechanism. As shown in previous work (Gelin & Karplus, 1977), the proximal histidine serves as the link between the position of the heme and the F-helix; the asymmetric orientation of the histidine in the deoxy structure, coupled with contributions from other heme-protein interactions, appears to initiate the tertiary structural changes induced by ligand binding. The reduced oxygen affinity of hemoglobin results not from tension on the heme in the unliganded structure (there is none) but instead from strain in the liganded subunit of the tetramer within the deoxy quaternary structure.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Biol 1983 Dec 25
PMID:Hemoglobin tertiary structural change on ligand binding. Its role in the co-operative mechanism. 666 23

To see whether plasmid molecules in bacteria are equally partitioned or randomly distributed at cell division, the segregation properties of temperature sensitive replication mutants of the E. coli plasmid pSC101 were tested at non-permissive temperature. The results support the idea that at least unreplicated molecules are passively distributed and thus the Equipartition Model is unlikely even under physiological conditions if plasmids replicate randomly. Therefore, we developed a new model which involves the Random Replication Hypothesis and assumes that only the two products of the last plasmid replication event are actively partitioned into two daughter cells and the others are randomly distributed. Mathematical studies revealed that the incompatibility segregation rate predicted by this model fits the experimental data.
Mol Gen Genet 1982
PMID:Temperature sensitive replication plasmids are passively distributed during cell division at non-permissive temperature: a new model for replicon duplication and partitioning. 675 66

In an empirical evaluation of a qualitative approach to construction of phylogenetic trees from protein-electrophoretic data, we have employed Hennigian cladistic principles to generate molecular trees for water-fowl, rodents, bats, and other phylads. This procedure of tree construction is described in detail. Branching structures of molecular trees produced by three different algorithms were compared against those of "model" classifications previously proposed by other systematists. In each case, the qualitative cladistic trees provided fits to model phylogenies which were strong and as good or better than those resulting from phenetic-clustering or distance-Wagner trees based on manipulation of quantitative values in matrices of genetic distance. The qualitative Hennigian approach has several pragmatic (as well as theoretical) advantages for analyzing routine sets of electrophoretic data: (1) the analyses are simple and can be performed by hand; (2) they provide the researcher with a strong "feel" for the data; (3) additional data (from new loci or species) can readily be added to the tree without need to recalculate distance matrices; and (4) the qualitative output of the analyses explicitly defines character states along all branches of the tree, and hence affords a high degree of testability. However, these advantages are counterbalanced by a number of serious disadvantages which will likely limit the general applicability of this qualitative approach. These drawbacks are also discussed in detail. For a deeper appreciation of electrophoretic-based protein phylogenies, it is suggested that both quantitative phenetic and qualitative cladistic analyses be employed when possible, and that results of the two approaches be contrasted.
J Mol Evol 1983
PMID:An empirical evaluation of qualitative Hennigian analyses of protein electrophoretic data. 688 67

Half-of-the-sites reactivity in oligomeric enzymes has generally been accepted as evidence for structural asymmetry between subunits. However, we show that the symmetric two-state allosteric model [Monod, J., Wyman, J., & Changeux, J.-P. (1965) J. Mol. Biol. 12, 88-118] is quantitatively consistent with half-of-the-sites reactivity data for several hexameric and tetrameric enzymes. Specifically, the time courses for both the modification and the inactivation of glutamate dehydrogenase by glutamyl alpha-chloromethyl ketone and uridine diphosphoglucose dehydrogenase by 5-(iodoacetamidoethyl)aminonaphthalene-1-sulfonic acid are fit with just five parameters for each enzyme-modifier pair. In the case of glyceraldehyde-3-phosphate dehydrogenase, the time courses for modification of the yeast enzyme by iodoacetic acid and the rabbit-muscle enzyme by 3,3,3-trifluorobromoacetone are fit with the same model, and parameter values from these fits are used to generate theoretical inactivation curves which are found to agree well with the experimentally measured inactivation. We conclude that half-of-the-sites reactivity, if it is not an artifact of residual heterogeneity, could be a kinetic phenomenon related to metastability of partially modified states of a symmetric oligomer and that asymmetry between subunits should therefore not necessarily be inferred from such behavior. If similar metastability occurs in substrate binding, it may play a significant role in mechanism of catalysis and control. In such cases, the virtual inaccessibility of the substrate binding equilibrium would preclude conventional quasi-equilibrium models for the enzyme kinetics.
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PMID:Molecular symmetry and metastable states of enzymes exhibiting half-of-the-sites reactivity. 702 97

Mannose is incorporated in monkey liver chromatin by the means of a nuclear membrane mannosyltransferase. 14C-labelled chromatin is dissociated either by sulfuric acid or 6 M urea and 0.4 M GuCl. The fractions then enriched in non-histone 14C-labelled proteins are excluded from Ultro-gel AcA 202, their analysis in SDS-polyacrylamide gel electrophoresis shows that radioactivity fits with one major protein band, confirming the presence of at least a non-histone protein labelled with mannose in monkey liver chromatin, with an apparent molecular weight of 13,000.
Mol Cell Biochem 1982 Apr 16
PMID:Evidence of the mannosylation of a non-histone protein in monkey liver chromatin. 708 61

Computer simulation of protein evolution is based on a simple model consisting of random fixation of allowed codons (RFAC). Random replacement of single nucleotides occurs in a DNA sequence. If this results in any of the synonomous codons for allowed amino acids the mutation is fixed, if not, there is no change in the DNA and the cycle is repeated. Multiple fixations at the same nucleotide site, back mutations, degenerate fixations and coincidental identity of amino acids all occur. RFAC simulation begins with a single DNA sequence and follows a phylogeny based on the fossil record. The rate of fixation at the level of DNA is constant. The model upon which RFAC simulation is based is the same as the neutral theory of molecular evolution. The simulation is therefore a test of this theory. The results of simulated and real evolution are compared for fibrinopeptides A in mammals and cytochromes C and hemoglobin alpha and beta chains in vertebrates. In each case the allowed variation at each site has been set equal to that observed, twice that observed and all protein amino acids. Rates of fixation vary from 2.4 X 10(-10) to 10(-8) accepted nucleotide fixations per codon per year. There is some, although never excellent, agreement between real and simulated evolution, the better fits are obtained in the cases of fibrinopeptides A and cytochromes C. The major source of discrepancy between real evolution and simulation is irregularities in the rates of real evolution. RFAC simulation is compared with the random evolutionary hit (REH) model, augmented maximum parsimony and the accepted point mutations (PAM) approach.
J Mol Evol 1981
PMID:Simulation of protein evolution by random fixation of allowed codons. 728 88

In response to criticism of REH theory (Fitch 1980), Holmquist and Jukes (1981) have mostly avoided the criticism or misunderstood it. Since they themselves state in their response that "Amino acid sequence data alone cannot be used to estimate total nucleotide substitutions," they agree with the criticism. Most of their paper treats the newer theory (here designated as the REHN theory) which attempts to use the nucleotide sequences encoding proteins to better estimate total nucleotide substitutions (Holmquist and Pearl 1980). Since I made no criticism of REHN theory, their comments are frequently beside the point of my original criticism of REH theory. Nevertheless, it is shown here that REHN theory is also unsatisfactory in that: One, the varions are now more clearly defined but in such a way as to preclude the same codon from suffering a nucleotide substitution in more than one evolutionary interval. Two, the set of codons that accepts silent substitutions is identical to the set that accepts amino acid changing nucleotide substitutions. Three, the uncertainty in the REH estimate is considerable in that alternative excellent fits to the same observational data may give alternative REH values that differ significantly even before stochastic variation and selective bias are considered. Four, the fit of their model to data is an irrelevancy where there are zero degrees of freedom.
J Mol Evol 1981
PMID:The old REH theory remains unsatisfactory and the new REH theory is problematical - a reply to Holmquist and Jukes. 733 29

Acute exposure to hydrazine (N2H4), Mol. Wt.: 32.05, an importance liquid rocket propellant and parent compound of useful pharmaceutical agents such as isoniazid and hydralazine and other chemical compounds, produces severe central nervous system effects, such as coma and convulsions sometimes resulting in death. Heretofore, treatment has been symptomatic, e.g. quick-acting barbiturates for convulsions. The results of this study emphasize the importance of acute ammonia intoxication as a major component of the metabolic effects of hydrazine. Further, the results support the theory of competitive inhibition of ammonia by hydrazine (3).
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PMID:The importance of ammonia in the metabolic effects of hydrazine. 741 61

Thermal unfolding of the tryptic fragment of the membrane-bound protein, cytochrome b5, which contains the residues 1-90, was investigated by scanning calorimetry, circular dichroism and absorption spectroscopy. The fragment undergoes a reversible two-state transition at about 70 degrees C (neutral pH). The fragment exhibits all the thermodynamic properties of small globular proteins with respect to heat capacity and transitional changes of enthalpy, Gibbs energy and heat capacity. The heat capacity change at unfolding fits into the correlation with the specific amount of nonpolar contacts, which has been found to be valid for small globular proteins (Privalov, P.L. and Khechinashvili, N.N. (1974) J. Mol. Biol. 86, 665-684). The relatively low stabilization energy of the cytochrome b5 fragment (delta trsG25 degrees C = 25 kJ/mol) is discussed in terms of the functional requirements of electron-transfer proteins.
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PMID:Thermodynamic investigations of cytochrome b5 unfolding. I. The tryptic fragment of cytochrome b5. 745 84


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