Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight proteins of diverse lengths, functions, and origin, are examined for compositional non-randomness amino acid by amino acid. The proteins investigated are human fibrinopeptide A, guinea pig Insulin, rattlesnake cytochrome c, MS2 phage coat protein, rabbit triosephosphate isomerase, bovine pancreatic deoxyribonuclease A, bovine glutamate dehydrogenase, and Bacillus thermoproteolyticus thermolysin. As a result of this study the experimentally testable hypothesis is put forth that for a large class of proteins the ratio of that fraction of the molecule which exhibits compositional non-randomness to that fraction which does not is on the average, stable about a mean value (estimated as 0.32 plus or minus 0.17) and (nearly) independent of protein length. Stochastic and selective evolutionary forces are viewed as interacting rather than independent phenomena. With respect to amino acid composition, this coupling ameliorates the current controversy over Darwinian vs. non-Darwinian evolution, selectionist vs. neutralist, in favor of neither: Within the context of the quantitative data, the evolution of real proteins is seen as a compromise between the two viewpoints, both important. The compositional fluctuations of the electrically charged amino acids glutamic and aspartic acid, lysine and arginine, are examined in depth for over eighty protein families, both prokaryotic and eukaryotic. For both taxa, each of the acidic amino acids is present in amounts roughly twice that predicted from the genetic code. The presence of an excess of glutamic acid is independent of the presence of an excess of aspartic acid and vice versa.
J Mol Evol 1975 Mar 24
PMID:Deviations from compositional randomness in eukaryotic and prokaryotic proteins: the hypothesis of selective-stochastic stability and a principle of charge conservation. 17 58

Glucokinase from baker's yeast has been purified to homogeneity. The molecular weight of the subunit is 51,000. The native enzyme sediments with S20,w values in the range of 19 to nearly 4S. The presence of glucose and phosphate favors the heavier species while ATP causes depolymerization. Titration experiments with the Ellman reagent support this view. The enzyme subunit has four sulfhydryl residues of which one is more reactive than the other three. However, it does not seem to be directly responsible for the catalytic activity. The amino acid composition of the enzyme is similar to those of the hexokinases P1 and P2 but for aspartic acid and histidine.
Mol Cell Biochem 1977 Nov 25
PMID:Molecular properties of yeast glucokinase. 34 Sep 36

The amino-acid compositions of the mitochondrial ribosomal subunits of Saccharomyces cerevisiae have been determined and compared to those of cytoplasmic ribosomal subunits. For the large subunits, the mitochondrial and cytoplasmic ribosomes showed major differences in the proportions of arginine, alanine and methionine. For the small subunits, arginine, aspartic acid, alanine, valine and methionine showed marked differences. We have compared these amino-acid compositions with those already published of bacterial and eukaryotic ribosomes by a statistical method of data analysis. It appeared clearly that the yeast mitoribosomes are more distant from bacterial ribosomes than from eukaryotic cytoribosomes.
Mol Gen Genet 1979 Mar 27
PMID:Comparison of amino acid compositions of mitochondrial and cytoplasmic ribosomal proteins of Saccharomyces cerevisiae. 37 18

A model for the structure and function of extracellular carboxyl (acid) proteases can be established from three amino acid sequences and four crystal structures of these enzymes. The carboxyl proteases from gastric and fungal origins are very homologous in both primary and tertiary structures. The molecules consist of about 320 residues organized with a secondary structure which is primarily comprised of beta-strands and very similar tertiary structures. An apparent binding cleft, which can accommodate a substrate with about eight amino acid residues, contains near its midpoint the active center residues Asp-215, Asp-32, and Ser-35. These three residues are hydrogen bonded to each other. An intracellular carboxyl protease, cathepsin D, is very homologous to the extracellular enzymes in N-terminal amino acid sequence and primary structure location of active center residues. The tertiary structure of cathepsin D is probably similar, as well. However, cathepsin D contains a unique hydrophobic "tail" made up of about 100 residues added on the C-terminal side. Cathepsin D precursor is over 100,000 daltons in molecular weights, as contrasted to the gastric carboxyl protease zymogens, which are about 40,000 daltons. Carboxyl proteases contain two lobes symmetrical in peptide chain conformations. Each of the lobes also consists of two homologous structural units. These structural characteristics suggest that the original gene was coded for only about eighty amino acid residues and that gene duplication and fusion has taken place twice to produce a single chain carboxyl protease with four basic structural units in two symmetrical lobes. The formation of the zymogens and the cathepsin D "tail" must have resulted from various gene fusions. Partial sequence comparisons also suggest that cathepsin D may be an evolutionary ancestral chain for gastric carboxyl proteases.
Mol Cell Biochem 1979 Jul 31
PMID:Evolution in the structure and function of carboxyl proteases. 38 85

The three-dimensional crystal structure of bovine trypsinogen at approximately pH 7.5 was initially solved at 2.6 A resolution using the multiple isomorphous replacement method. Preliminary refinement cycles of the atomic coordinates trypsinogen have been carried out first to a resolution of 2.1 A, and later to 1.9 A, using constrained difference Fourier refinement; During the process, structure factors Fc and phi c were calculated from the trypsinogen structure and final interpretation was based on an electron-density map computed with terms (2 Fo - Fc) and phases phic at a resolution of 1.9 A. Crystals of trypsinogen grown from ethanol-water mixtures are trigonal with space group P3121, and cell dimension a = 55.17 A and c = 109.25 A. The structure is compared with the bovine diisopropylphosphoryltrypsin structure at approximately pH 7.2, oirginally determined from orthohombic crystals by Stroud et al. (Stroud, R.M., Kay L.M., and Dickerson, R.E. (1971), Cold Spring Harbor Symp. Quant. Biol. 36, 125-140; Stroud, R.M., Kay, L.M., and Dickerson, R.E. (1974), J. Mol. Biol. 83, 185-208), and later refined at 1.5 A resolution by Chambers and Stroud (Chambers, J.L., and Stroud, R.M. (1976), Acta Crystallogr. (in press)). At lower pH, 4.0-5.5 diogen, with cell dimensions a = 55.05 A and c = 109.45 A. This finding was used in the solution of the six trypsinogen heavy-atom derivatives prior to isomorphous phase analysis, and as a further basis of comparison between trypsinogen and the low pH trypsin structure. There are small differences between the two diisopropylphosphoryltrypsin structures. Bovine trypsinogen has a large and accessible cavity at the site where the native enzyme binds specific side chains of a substrate. The conformation and stability of the binding site differ from that found in trypsin at approximately pH 7.5, and from that in the low pH form of diisopropylphosphoryltrypsin. The catalytic site containing Asp-102, His-57, and Ser-195 is similar to that found in trypsin and contains a similar hydrogen-bounded network. The carboxyl group of Asp-194, which is salt bridged to the amino terminal of Ile-16 in native trypsin or other serine proteases, is apparently hydrogen bonded to internal solvent molecules in a loosely organized part of the zymogen structure. The unusually charged N-terminal hexapeptide of trypsinogen, whose removal leads to activation of the zymogen, lies on the outside surface of the molecule. There are significant structural changes which accompany activation in neighboring regions, which include residues 142-152, 215-550, 188A-195. The NH group of Gly-193, normally involved in stabilization of reaction intermediates (Steitz, T.A., Henderson, R., and Blow, D.M. (1969), J. Mol. Biol. 46, 337-348; Henderson, R. (1970), J. Mol. Biol. 54, 341-354; robertus, J.D., Kraut, J., Alden, R.A., and Birkoft, J.J. (1972), Biochemistry 11, 4293-4303) in the enzyme, is moved 1.9 A away from its position in trypsin...
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PMID:Structure of bovine trypsinogen at 1.9 A resolution. 55 51

Using quantitative gel filtration techniques partition coefficients, Kp-values, have been determined between aqueous cationic micellar hexadecyltrimethylammonium bromide, CTAB, and several biomonomer. Kp-values for 5'-adenylic acid, 5'-cytidylic acid, 5'-guanylic acid, 5'-uridylic acid and 5'-thymidylic acid are 1,400 +/- 150. Nucleotides bind to CTAB micelles effectively, but nonselectively. Conversely, the binding of tRNAs to micellar CTAB is selective. Kp-values for glutamic acid II, tyrosine and phenylalanine tRNAs (in 1.0MNaCl) are 520, 3,100 and 5,600, respectively. Kp-values for the binding of alanine, arginine, aspartic acid, glutamic acid, glycine, histidine, phenylalanine, serine, threonine and tryptophan to micellar CTAB are less than 8. Conversion of unitless Kp-values for the binding of amino acids, nucleotides and nucleosides to both anionic and cationic micelles, to K (in 1/g) values allows the comparison of clays and micelles as prebiotic concentrating media. Using correlations between surface densities of the biomonomers and their binding constants, it is shown that aqueous micelles (at pH = 8) are a better concentrating media than are clays.
J Mol Evol 1977 Dec 29
PMID:Partitioning of amino acids and nucleotides between water and micellar hexadecyltrimethylammonium halides. The prebiotic significance of cationic surfaces. 59 74

Internal regularities of amino acid sequences of flavodoxins, FMN-containing, low molecular weight flavoproteins, were statistically examined using the minimum mutation method. The sequence of Clostridium pasteurianum flavodoxin shows statistically significant evidence of repetitious internal gene duplications at different levels of structure. Peptide pairs with a low chance probabilitiy of occurrence were frequently observed at a shift of 5 residues. The pairs with the lowest chance probabilities are a pair of heptapeptides at positions39--45 vs. 44--50, a 5 residue shift (p = 9 x 10(-6)). Most of the related pairs are consistent and could best be explained by the repeating pentapeptide sequence: (Lys-Gly-Ala-Asp-Val-)n and appropriate gaps. Internal repetitions with longer shifts were also suggested for other flavodoxins. Repetitious gene duplication is proposed for the early stages of flavodoxin evolution.
J Mol Evol 1978 Aug 02
PMID:The evolution of protein sequences by repetitious gene duplication: clostridial flavodoxin. 69 Oct 74

1. A jejunal perfusion technique has been used in normal volunteer subjects to study jejunal absorption of amino acid residues from a partial enzymic hydrolysate of casein in which about 50% of the amino acids existed as small peptides, and also from an equivalent mixture of free amino acids. 2. The effect of a high concentration of the dipeptide glycylglycine on the absorption of amino acid residues from these preparations was studied to quantify the importance of mucosal uptake of intact peptides during absorption of the partial hydrolysate of casein. 3. The results were unexpected. Glycylglycine significantly inhibited absorption of several amino acid residues (aspartic acid + asparagine, serine, glutamic acid + glutamine, proline, alanine, phenylalanine, threonine and isoleucine) from the free amino acid mixture, whereas it significantly inhibited the absorption of only two (serine, glutamin acid + glutamine) from the peptide-containing partial casein hydrolysate. 4. The effect of glycylglycine on absorption of amino acids from the mixture of free amino acids was apparently due to inhibition of amino acid uptake by free glycine liberated from the dipeptide during perfusion. The reason for the failure of glycylglycine to cause extensive inhibition of absorption from the partial hydrolysate is not clear. It may be due to glycylglycine being only a weak inhibitor of peptide uptake, but the possibility that some peptides are taken up by a system unavailable to glycylglycine has to be considered.
Clin Sci Mol Med 1977 Jul
PMID:Effect of glycylglycine on absorption from human jejunum of an amino acid mixture simulating casein and a partial enzymic hydrolysate of casein containing small peptides. 87 18

The constants of inhibition by the nucleotides and constituting components catalysed by intracellular "acid" (pHopt 4.7), non-specific RNAse from Asp. clavatus (EC 3.1.4.23) were determined.. All the nucleotides were found to be competitive inhibitors. The influence of composition and structure of the nucleotides on their interaction with the active site of RNAse is discussed.
Mol Biol (Mosk)
PMID:[Inhibition of Aspergillus clavatus intracellular RNA-ase by nucleotides and the components comprising them]. 95 25

The primary structure of the major component of human skeletal muscle troponin C has been established. The troponin C was purified by ammonium sulphate and isoelectric fractionation, followed by two chromatographic steps on DEAE Sephadex. The sequence was determined from the different overlapping enzymic peptides and by dansyl-Edman degradation. The only difference between rabbit skeletal muscle troponin C and the major component of human skeletal troponin C was found at position 112: Ala (rabbit), Pro (human). The partial amino acid sequence of the first 86 residues of the minor component of human skeletal troponin C was found to resemble the troponin C from bovine cardiac muscle. The only difference between them, has tentatively been located at position 62: Glu (human), Asp (bovine). These similarities suggest that troponin C is, from the point of view of molecular, one of the most conservative proteins so far studied.
J Mol Evol 1976 Oct 27
PMID:Human skeletal muscle proteins. The primary structure of troponin C. 97 49


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