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Query: UNIPROT:P06889 (Mol)
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The fetal globin genes G gamma and A gamma from one chromosome of a chimpanzee (Pan troglodytes) were sequenced and found to be closely similar to the corresponding genes of man and the gorilla. These genes contain identical promoter and termination signals and have exons 1 and 2 separated by the conserved short intron 1 (122 bp) and exons 2 and 3 separated by the more rapidly evolving, larger intron 2 (893 bp and 887 bp in chimpanzee G gamma and A gamma, respectively). Each intron 2 has a stretch of simple sequence DNA (TG)n serving possibly as a "hot spot" for recombination. The two chimpanzee genes encode polypeptide chains that differ only at position 136 (glycine in G gamma and alanine in A gamma) and that are identical to the corresponding human chains, which have aspartic acid at position 73 and lysine at 104 in contrast to glycine and arginine at these respective positions of the gorilla A gamma chain. Phylogenetic analysis by the parsimony method revealed four silent (synonymous) base substitutions in evolutionary descent of the chimpanzee G gamma and A gamma codons and none in the human and gorilla codons. These Homininae (Pan, Homo, Gorilla) coding sequences evolved at one-tenth the average mammalian rate for nonsynonymous and one-fourth that for synonymous substitutions. Three sequence regions that were affected by gene conversions between chimpanzee G gamma and A gamma loci were identified: one extended 3' of the hot spot with G gamma replaced by the A gamma sequence, another extended 5' of the hot spot with A gamma replaced by G gamma, and the third conversion extended from the 5' flanking to the 5' end of intron 2, with G gamma replaced here by the A gamma sequence. A conversion similar to this third one has occurred independently in the descent of the gorilla genes. The four previously identified conversions, labeled C1-C4 (Scott et al. 1984), were substantiated with the addition of the chimpanzee genes to our analysis (C1 being shared by all three hominines and C2, C3, and C4 being found only in humans). Thus, the fetal genes from all three of these hominine species have been active in gene conversions during the descent of each species.
Mol Biol Evol 1985 Sep
PMID:Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution. 387 Aug 67

Ab initio quantum mechanical calculations have been used to obtain details of the electron density distribution in a high-resolution refined protein structure. It is shown that with accurate atomic co-ordinates, electron density may be calculated with a quality similar to that which can be obtained directly from crystallographic studies of small organic molecules, and that this density contains information relevant to the understanding of catalysis. Atomic co-ordinates from the 1.8 A and 1.5 A resolution refinements of the crystal structure of protease A from Streptomyces griseus have been used to examine the influence of the environment on the electron density in the side-chain of the active site histidine (His57). The neighbouring aspartic acid 102 is the dominant factor in the environment, and quantum mechanical calculations have been performed on these two residues. Most interesting from the point of view of understanding the catalytic process is the effect that Asp102 has on the electron density in the region of the imidazole nitrogen (N epsilon 2) adjacent to the active site serine 195. In the positively charged imidazolium species, there is a polarization of the N epsilon 2-H bond, reducing the bonding density in a manner that may lower the height of the energy barrier for proton transfer. In the uncharged imidazole species, the proximity of Asp102 causes a movement of density from the lone pair region of the N epsilon 2 into the pi bonding region above and below the plane of the ring. Although it is shown that the primary effect of the aspartic acid is electrostatic, this movement is perpendicular to the direction of the electric field inducing it.
J Mol Biol 1985 Apr 20
PMID:Electron density calculations as an extension of protein structure refinement. Streptomyces griseus protease A at 1.5 A resolution. 389 15

The structure of yeast transfer RNA aspartic acid has been refined in one crystal form to 3 A resolution using the restrained least-squares method of Hendrickson and Konnert and real-space fitting using the FRODO program of Jones. The final crystallographic discrepancy index R is 23.5% for 4585 reflections with magnitudes twice their standard deviations between 10 and 3 A. With lower occupancies for some residues of the D-loop, the phosphate U1, and the base U33, the R-factor is 22.3%. The adaptation of the restrained least-squares program for nucleic acids and the progress of the refinement are described. The conformations are analysed with respect to stereochemistry and folding of the backbone. The contacts and hydrogen bonds of the secondary structure are compared with those of yeast tRNAPhe. The presence of only four bases in the variable loop, instead of five as in yeast tRNAPhe, leads to a rotation of residue 48 and a lateral movement of residue 46. These two rearrangements induce different environments for [U8 . . . A14] . . . A21 as well as for A9 and G45. Otherwise, all tertiary contacts observed in yeast tRNAPhe are present in yeast tRNAAsp, except for the absence of hydrogen-bonding between G18 of the D-loop and C56 of the T-loop. The presence of anticodon triplet pairing leads to a distribution of temperature factors different from that observed in yeast tRNAPhe with a stabilization of the AC stem-and-loop and a destabilization of the T and D-loops. We are inclined to suggest that the labilization of the interactions between the T and D-loops is a consequence of the interaction of the anticodon triplets of symmetry-related molecules through hydrogen bonding, which mimics the interaction between the anticodon and its cognate codon on the messenger RNA.
J Mol Biol 1985 Jul 05
PMID:Crystallographic refinement of yeast aspartic acid transfer RNA. 389 53

The frequencies of occurrence of nucleotides at the 5' side of codons have been determined in highly and weakly expressed genes from E. coli. Significant constraints on the nucleotide 5' to some codons were found in highly expressed genes. Certain rules of synonymous codon usage depending on the amino acid 3' of the codon were established. E. g., codon possessing quanosine in the third position (NNG) are preferred over NNA if the next amino acid is lysine (P less than 10(-5)). On the other hand, rules of synonymous codon usage in relation to 5' flanking nucleotide were found. For example, when coding for aspartic acid, GAC codon is preferred over GAU (P less than 0.001) if uridine is 5' to codon and on the contrary GAU is favoured (P less than 0.0001) if quanosine is at the 5' side of aspartic acid codon. These rules can be used in the chemical synthesis of genes designed for expression in E. coli.
Mol Biol (Mosk)
PMID:[Regularities of the nucleotide sequence at the 5'-end of the codon in Escherichia coli genes]. 390 Jun 92

Detailed structure of the pepsin active site in the region of the active aspartic acid residues and substrate binding S1 and S1' sites is considered. At the active site of the enzyme crystals studied several molecules of ethanol were detected, which interact with active groups. The catalytic properties of aspartyl proteinases towards dipeptide substrates were explained on the base of the specific structure of S1 and S1' binding sites.
Mol Biol (Mosk)
PMID:[The structure of pepsin. II. Structure of the enzyme active site (at 2 angstroms resolution)]. 392 May 6

Proton NMR spectra of serine proteases in 1H2O solutions typically show a single resonance at very low magnetic field--i.e., 14-18 ppm from dimethylsilylapentanesulfonate. This resonance has been assigned to the proton hydrogen bonded between aspartic acid-102 and histidine-57 (chymotrypsin numbering system) of the "charge-relay system" or catalytic triad of serine proteases [Robillard, G. & Shulman, R. G. (1972) J. Mol. Biol. 71, 507-511]. Since then, there have been a number of reports that have cast doubt on its correctness. In the present work we have tested this assignment using alpha-lytic protease (EC 3.4.21.12, Myxobacter alpha-lytic proteinase), a bacterial serine protease homologous to elastase, which is specifically labeled with nitrogen-15 at N delta 1 of its single histidine residue. The low-field region of the proton spectra of this labeled enzyme shows a single resonance having the properties reported [Robillard, G. & Shulman, R. G. (1974) J. Mol. Biol. 86, 519-540], which, in addition, exhibits spin-spin splitting to the nitrogen-15 label. The observation of this 15N delta 1-H coupling makes the assignment of this resonance to the charge-relay proton unequivocal.
 ...
PMID:Confirmation of the assignment of the low-field proton resonance of serine proteases by using specifically nitrogen-15 labeled enzyme. 393 65

To examine in detail a class of peptides that inhibit the polymerization of deoxyhemoglobin S, we assayed the L-amino acids and 22 dipeptides for their effect on deoxyhemoglobin S solubility. Of the amino acids, the aromatics (phenylalanine, tyrosine, and tryptophan) significantly increased deoxyhemoglobin S solubility, as did high concentration of arginine. Combinations of the hydrophobic (specifically the aromatic) amino acids with a hydrophilic amino acid, such as arginine or lysine, resulted in dipeptides which were much more soluble than the hydrophobic or aromatic amino acid alone, and also inhibited polymerization. Furthermore, samples of deoxyhemoglobin S at 26 to 27 g/dl containing some of these dipeptides such as Arg-Trp, Arg-Phe, and Lys-Trp in excess of 50 to 100 mM did not polymerize, indicating a 1.4- to 1.6-fold increase in deoxyhemoglobin S solubility. The enhancement of polymerization, i.e., decrease in deoxyhemoglobin S solubility, observed by the addition of aspartic acid, glycine, or lysine was observed or was reduced in the dipeptides containing these hydrophilic amino acids combined with hydrophobic amino acids (valine, leucine, isoleucine, or the aromatic amino acids). The effects of these dipeptides on deoxyhemoglobin S solubility were mostly linear with concentration. However, the changes in deoxyhemoglobin S solubility by addition of a dipeptide was not simply the sum of the effects observed with the individual amino acids as exemplified by the differential effect of reversing the dipeptide sequence (e.g., Arg-Phe and Phe-Arg, or Arg-Tyr and Tyr-Arg). These data provide further evidence as to the stereospecific nature of this class of noncovalent inhibitors of deoxyhemoglobin S polymerization.
Mol Pharmacol 1985 Jul
PMID:Dipeptides as inhibitors of the gelation of sickle hemoglobin. 402 96

There are more than 20 beta-actin-specific sequences in the human genome, many of which are pseudogenes. To facilitate the isolation of potentially functional beta-actin genes, we used the new method of B. Seed (Nucleic Acids Res. 11:2427-2446, 1983) for selecting genomic clones by homologous recombination. A derivative of the pi VX miniplasmid, pi AN7 beta 1, was constructed by insertion of the 600-base-pair 3' untranslated region of the beta-actin mRNA expressed in human fibroblasts. Five clones containing beta-actin sequences were selected from an amplified human fetal gene library by homologous recombination between library phage and the miniplasmid. One of these clones contained a complete beta-actin gene with a coding sequence identical to that determined for the mRNA of human fibroblasts. A DNA fragment consisting of mostly intervening sequences from this gene was then used to identify 13 independent recombinant copies of the analogous gene from two specially constructed gene libraries, each containing one of the two types of mutant beta-actin genes found in a line of neoplastic human fibroblasts. The amino acid and nucleotide sequences encoded by the unmutated gene predict that a guanine-to-adenine transition is responsible for the glycine-to-aspartic acid mutation at codon 244 and would also result in the loss of a HaeIII site. Detection of this HaeIII polymorphism among the fibroblast-derived clones verified the identity of the beta-actin gene expressed in human fibroblasts.
Mol Cell Biol 1984 Oct
PMID:Molecular cloning and characterization of mutant and wild-type human beta-actin genes. 609 33

gamma-Glutamylamine cyclotransferase, an enzyme found in a number of animal tissues and cells, catalyzes the conversion of epsilon-(L-gamma-glutamyl)-L-lysine to free lysine and 5-oxo-L-proline as well as the release of free amines and the formation of 5-oxo-L-proline from a variety of other L-gamma-glutamylamines. Among its substrates are both the mon- and di-gamma-glutamyl derivatives of putrescine, spermidine and spermine, and a derivative of epsilon-(L-gamma-glutamyl)-L-lysine in which both the alpha-amino group and the carboxyl group of the lysine moiety are blocked. The enzyme does not act on most gamma-glutamyl-alpha-amino acids, nor is it active toward the epsilon-lysyl derivatives of L-aspartic acid or D-glutamic acid. Derivatives of epsilon-(L-gamma-glutamyl)-L-lysine in which the alpha-amino or the alpha-carboxyl function of the glutamyl moiety is blocked also do not serve as substrates. The specificity of gamma-glutamylamine cyclotransferase is in accordance with the proposal that it functions biologically in the latter stages of the catabolism of products of the action of transglutaminases. Some suggestions as to the manner in which gamma-glutamylamine cyclotransferase serves this function are made based on present knowledge of protein degradation.
Mol Cell Biochem 1981 Aug 11
PMID:gamma-Glutamylamine cyclotransferase. An enzyme involved in the catabolism of epsilon-(gamma-glutamyl)lysine and other gamma-glutamylamines. 611 8

The experiments were carried out to find out whether exogenous glutamic or aspartic acid could diminish changes in the cardiac contractile function and high-energy phosphate content caused by underperfusion of isolated isovolumic rat heart. After 40 min of reduced coronary flow (from 10 to 3 ml/min) there was an almost four-fold fall in the developed pressure, and more than three-fold rise in the diastolic pressure as well as a profound fall in creatine phosphate (CP) and ATP content. Glutamic (68 mM) or aspartic (75 mM) acids were added to the perfusate after 10 min of underperfusion when the developed pressure had declined almost to the same level as was observed after 40 min and the content of CP was reduced more than two-fold. Glutamic acid completely prevented the rise in the diastolic pressure and significantly increased the CP content, as compared to its level observed before addition of glutamate, but glutamic acid did not change the developed pressure. As a result, the CP and ATP contents were three- and two-fold higher, respectively, after addition of glutamic acid as compared to control underperfused hearts. Similar, but slightly less prominent effects were observed when aspartic acid was added instead of glutamic acid. These results suggest that high concentrations of glutamic and aspartic acids can exert beneficial effects on ischemic heart muscle.
J Mol Cell Cardiol 1983 Jan
PMID:Effect of glutamic and aspartic acids on adenine nucleotides, nitrogenous compounds and contractile function during underperfusion of isolated rat heart. 613 4


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