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

Cytoplasmic monomeric hemoglobin I from the bacteria-harboring gill of the bivalve mollusc Lucina pectinata has been crystallized in a form suitable for atomic resolution X-ray structural investigations. The crystals have been grown at pH 4.8, in 0.05 M-acetate buffer, using 2.6 M-ammonium sulfate as precipitating agent. The crystals belong to the monoclinic space group P2(1), with unit cell constants a = 50.0 A, b = 38.6 A, c = 42.1 A, beta = 107.1 degrees, and contain one molecule (14,000 Mr) in the asymmetric unit. By means of single crystal microspectrophotometry it has been shown that the crystals contain the ferric form of L. pectinata "sulfide reactive" hemoglobin I. On the other hand, by careful control of the buffering medium composition, it has been possible to obtain stable crystals of the deoxy, oxy and sulfide forms of the protein.
J Mol Biol 1991 Dec 05
PMID:Crystallization and preliminary data for the ferric form of Lucina pectinata hemoglobin I. 174 87

Diffraction data to 3.1 A resolution were collected on crystals of a complex of components II and III of the cytoplasmic hemoglobin of the symbiont-harboring clam Lucina pectinata. The crystal system is tetragonal, a = 76.3 A, c = 153.1 A and the space group is P42212. The asymmetric unit probably contains a dimer of the tetrameric complex.
J Mol Biol 1991 Dec 05
PMID:Crystallization of a complex of hemoglobin components II and III of the symbiont-harboring clam Lucina pectinata. 174 91

A novel multivariate statistical approach is presented for extracting and exploiting intrinsic information present in our ever-growing sequence data banks. The information extraction from the sequences avoids the pitfalls of intersequence alignment by analyzing secondary invariant functions derived from the sequences in the data bank rather than the sequences themselves. Such typical invariant function is a 20 x 20 histogram of occurrences of amino acid pairs in a given sequence or fragment thereof. To illustrate the potential of the approach an analysis of 10,000 protein sequences from the National Biomedical Research Foundation Protein Identification Resource is presented, whose analysis already reveals great biological detail. For example, zeta-hemoglobin is found to lie close to amphibian and fish chi-hemoglobin which, in turn, is an important clue to the physiological function of this mammalian early embryonic hemoglobin. The multivariate statistical framework presented unifies such apparently unrelated issues as phylogenetic comparisons between a set of sequences and distance matrices between the constituents of the biological sequences. The Multivariate Statistical Sequence Analysis (MSSA) principles can be used for a wide spectrum of sequence analysis problems such as: assignment of family memberships to new sequences, validation of new incoming sequences to be entered into the database, prediction of structure from sequence, discrimination of coding from non-coding DNA regions, and automatic generation of an atlas of protein or DNA sequences. The MSSA techniques represent a self-contained approach to learning continuously and automatically from the growing stream of new sequences. The MSSA approach is particularly likely to play a significant role in major sequencing efforts such as the human genome project.
J Mol Biol 1991 Aug 20
PMID:A new family of powerful multivariate statistical sequence analysis techniques. 188 Aug 2

The first section of this publication summarizes early work according to which 5 beta-pregnanedione is an important metabolite of progesterone in the early stages of the chick embryo's adrenal steroidogenesis, then decreasing gradually as corticosteroidogenesis increases. In the second section a model is described in which adrenal 3 beta-ol hydroxylase-isomerase of the 17-day-old chicken is suppressed pharmacologically, this suppression being correlated with that of the synthesis of aminoevulinic acid (ALA), the first and rate-limiting step of the heme pathway. 5 beta-Pregnanedione (10(-7)-10(-6) M) restored ALA synthesis in this inhibited model to normal values. The effect of 5 beta-pregnanedione was specific since other steroids tested: progesterone; 5 alpha-pregnanedione; corticosterone or estradiol, did not stimulate ALA. Since heme formation by steroidogenic glands contributes to the synthesis of cytochrome P450 rather than hemoglobin, 5 beta-pregnanedione was also assayed as a stimulator of this enzyme system and was found to increase cytochrome P450 in adrenals and testes but not in the liver. In view of these results a hypothesis is advanced according to which 5 beta-reduced progestagens and androgens stimulate cytochrome P450 formation, i.e. the synthesis of progesterone and higher hydroxylated steroids, by steroidogenic glands in the event of an excessive precursor reduction.
J Steroid Biochem Mol Biol 1991 Aug
PMID:Regulatory effects of 5 beta-reduced steroids. 188 86

Carbonmonoxy hemoglobin Ypsilanti (beta 99 Asp-Tyr) exhibits a quaternary form distinctly different from any structures previously observed for human hemoglobins. The relative orientation of alpha beta dimers in the new quaternary form lies well outside the range of values observed for normal unliganded and liganded tetramers (Baldwin, J., Chothia, C., J. Mol. Biol. 129:175-220, 1979). Despite this large quaternary structural difference between carbonmonoxy hemoglobin Ypsilanti and the two canonical structures, the new quaternary structure's hydrogen bonding interactions in the "switch" region, and packing interactions in the "flexible joint" region, show noncovalent interactions characteristic of the alpha 1 beta 2 contacts of both unliganded and liganded normal hemoglobins. In contrast to both canonical structures, the beta 97 histidine residue in carbonmonoxy hemoglobin Ypsilanti is disengaged from quaternary packing interactions that are generally believed to enforce two-state behavior in ligand binding. These features of the new quaternary structure, denoted Y, may therefore be representative of quaternary states that occur transiently along pathways between the normal unliganded, T, and liganded, R, hemoglobin structures.
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PMID:The mutation beta 99 Asp-Tyr stabilizes Y--a new, composite quaternary state of human hemoglobin. 189 30

The reaction of human hemoglobin with carbon monoxide has been investigated near the equilibrium isosbestic wavelength (i.e. 426 nm). As previously reported by others [Gray, R.D. & Gibson, Q. H. (1971) J. Biol. Chem. 246, 5176-5178], in the presence of 0.1 M phosphate pH 7.0 a rise-and-fall kinetic pattern can be observed at this wavelength, which indicates the presence of at least one spectroscopically detectable intermediate species. In this paper we demonstrate that (a) the intermediate species is thermodynamically stable; (b) both phases refer to bimolecular processes; (c) only the initial fast phase is observed when deoxyhemoglobin is reacted with substoichiometric amounts of CO (i.e. final [CO]/[heme] less than or equal to 0.5); (d) only the second slow phase is observed when hemoglobin that is partially saturated with CO (Y less than or equal to 0.5) is reacted with saturating CO concentrations; (e) the CO dissociation rate constant measured on the intermediate formed after a partial CO saturation at a final Y approximately 0.4 has a value similar to that observed starting from the fully liganded form. These results can be accounted for by a two-state allosteric model [Monod, J., Wyman, J. & Changeux, J.-P. (1965) J. Mol. Biol. 12, 88-118] under the assumption that either (a) 426 nm is an isosbestic wavelength for the T0-R spectral changes but not for the T0-T liganded reaction; or (b) a functional heterogeneity of the two types of subunits is present in the T state and at this wavelength this feature is spectroscopically detectable.
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PMID:Observation of a stable intermediate form in the reaction of human hemoglobin with carbon monoxide. 190 45

Purification of hemoglobin from North Atlantic salmon (Salmo salar) gave three different types. The CO-complexes of types I and III have been crystallized by the batch method at 4 degrees C from solutions 18% (w/v) in polyethylene glycol 2000, 50 mg/ml in hemoglobin and 0.05 M in phosphate buffer (pH 8.3). Orthorhombic crystals, space group P2(1)2(1)2(1), were obtained for both, with cell dimensions a = 53.9 A, b = 80.4 A, c = 132.4 A, and a = 58.7 A, b = 95.0 A, c = 107.4 A, for types I and III, respectively.
J Mol Biol 1991 Aug 20
PMID:Crystallization and preliminary X-ray crystallographic studies of CO-hemoglobin from the North Atlantic salmon (Salmo salar). 190 4

Assessment of the roles of the carboxyl-terminal beta 146 histidyl residues in the alkaline Bohr effect in human normal adult hemoglobin by high-resolution proton nuclear magnetic resonance spectroscopy requires assignment of the resonances corresponding to these residues. Previous resonance assignments in low ionic strength buffers for the beta 146 histidyl residue in the carbonmonoxy form of hemoglobin have been controversial [see Ho and Russu (1987) Biochemistry 26, 6299-6305; and references therein]. By a careful spectroscopic study of human normal adult hemoglobin, enzymatically prepared des(His146 beta)-hemoglobin, and the mutant hemoglobins Cowtown (beta 146His----Leu) and York (beta 146His----Pro), we have resolved some of these conflicting results. By a close incremental variation of pH over a wide range in chloride-free 0.1 M N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid buffer, a single resonance has been found to be consistently missing in the proton nuclear magnetic resonance spectra of these hemoglobin variants. The spectra of each of these variants show additional perturbations; therefore, the assignment has been confirmed by an incremental titration of buffer conditions to benchmark conditions, i.e., 0.2 M phosphate, where the assignment of this resonance is unambiguous. The strategy of incremental titration of buffer conditions also allows extension of this resonance assignment to spectra taken in 0.1 M [bis(2-hydroxyethyl)amino]tris(hydroxymethyl)methane buffer. Participation of the beta 146 histidyl residues in the Bohr effect has been calculated from the pK values determined for the assigned resonances in chloride-free 0.1 M N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid buffer. Our results indicate that the contribution of the beta 146 histidyl residues is 0.52 H+/hemoglobin tetramer at pH 7.6, markedly less than the 0.8 H+/hemoglobin tetramer estimated by study of the mutant hemoglobin Cowtown (beta 146His----Leu) by Shih and Perutz [(1987) J. Mol. Biol. 195, 419-422]. We have found that at least two histidyl residues in the carbonmonoxy form of this mutant have pK values that are perturbed, and we suggest that these pK differences may in part account for this discrepancy. Furthermore, summation of the positive contribution of the beta 146 histidyl residues and the negative contribution of the beta 2 histidyl residues to the maximum Bohr effect measured in 0.1 M N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid buffer suggests that additional sites in the hemoglobin molecule account for proton release upon ligation greater than the contribution of the beta 146 histidyl residues.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Roles of the beta 146 histidyl residue in the molecular basis of the Bohr effect of hemoglobin: a proton nuclear magnetic resonance study. 199 1

The human erythroleukemic cell line K562 was used as a model for analysis of the mechanisms responsible for alterations in gene expression during differentiation. K562 cells normally synthesize fetal hemoglobin (gamma-globin), but treatment with tumor-promoting phorbol esters (phorbol myristate acetate and tetradecanoyl phorbol acetate) results in the loss of the erythroid phenotype of the cells and causes a shift toward a megakaryocytic phenotype. This shift involves markedly decreased production of fetal hemoglobin and de novo synthesis of a number of proteins specific for megakaryocytes. The results of this work indicate that negative regulation of fetal hemoglobin during megakaryocytic differentiation of K562 cells occurs at the level of down regulation of gamma-globin mRNA accumulation. This effect consists of at least two components: reduction in the rate of transcription of the gamma-globin gene and decrease in stability of the normally very stable gamma-globin mRNA. We have developed two assay systems that permit investigation of the transcriptional and posttranscriptional effects of phorbol myristate acetate independently from each other. These assay systems make use of a heterologous reporter gene for the transcriptional analysis and a marked gamma-globin gene for the analysis of mRNA stability. The DNA sequences located in the 3' flanking region of the A gamma-globin gene were found to be responsible for the decrease in transcription rate.
Mol Cell Biol 1991 Jul
PMID:Negative regulation of globin gene expression during megakaryocytic differentiation of a human erythroleukemic cell line. 204 67

We report the low temperature carbon monoxide recombination kinetics after photolysis and the temperature dependence of the visible absorption spectra of the isolated alpha SH-CO and beta SH-CO subunits from human hemoglobin A in ethylene glycol/water and in glycerol/water mixtures. Kinetic measurements on sperm whale (Physeter catodon) myoglobin and previously published optical spectroscopy data on the latter protein and on human hemoglobin A, in both solvents, (Cordone, L., A. Cupane, M. Leone, E. Vitrano, and D. Bulone. 1988. J. Mol. Biol. 199:312-218) are taken as reference. Low temperature flash photolysis data are analyzed within the multiple substates model proposed by Frauenfelder and co-workers (Austin, R. H., K. W. Beeson, L. Eisenstein, H. Frauenfelder, and I. C. Gunsalus. 1975. Biochemistry. 14:5355-5373). Within this model a distribution of activation enthalpies for ligand binding accounts for the structural heterogeneity of the protein, while the preexponential factor, containing also the entropic contribution to the free energy of the process, is considered to be constant for all conformational substates. Optical spectra are deconvoluted in gaussian components and the temperature dependence of the moments of the resulting bands is analyzed, within the harmonic Frank-Condon approximation, to obtain information on the stereodynamic properties of the heme pocket. The kinetic and spectral parameters thus obtained are found to be protein dependent also with respect to their sensitivity to changes in the composition of the external medium. A close correlation between the kinetic and spectral features is observed for the proteins examined under all experimental conditions studied. The results reported are discussed in terms of differences in the heme pocket structure and in the conformational heterogeneity among the various proteins, as related to their different capability to accommodate constraints imposed by the external medium.
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PMID:Protein dynamics. Comparative investigation on heme-proteins with different physiological roles. 204 28


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