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)

We found a pentapeptide conformation, termed a type I twist, which has a strikingly high propensity (56%) for aspartic acid in the first position. Type I twists include the active site loops from cellular and viral aspartic proteases, with the catalytic Asp in the first position. Fifteen other type I twists, from non-homologous proteins, were found among high-resolution structures in the Protein Data Bank using a comparison method based on main-chain torsion angles. We propose that the Asp affects electrostatic interactions and thus plays a major structural role in the formation of this recurring motif, in addition to its catalytic role in the aspartic proteases.
J Mol Biol 1990 Nov 20
PMID:A common pentapeptide conformation occurs in viral acid proteases and other proteins. 225 19

The parasitic protozoa Leishmania are intracellular pathogens which enter host cells through largely undefined mechanisms. One molecule thought to play an important role in this process is gp63, the major glycoprotein on the surface of the infective promastigote form. We have cloned and analyzed the gp63 gene from Leishmania chagasi, an etiologic agent of acute visceral leishmaniasis. The predicted amino acid sequence is highly homologous to that reported for Leishmania major, with the exception of a 56-amino-acid region. This region in L. major was predicted to contain an arginine-glycine-aspartic acid (RGD) sequence that was subsequently hypothesized to be involved in binding to the host cell. The L. chagasi gene lacks this sequence or indeed any RGD sequence, and further studies failed to confirm the existence of an RGD sequence in the L. major gp63 gene. Binding to the host cell surface must therefore be mediated by other sequences in gp63 or by other components of the Leishmania promastigote.
Mol Biochem Parasitol 1990 Mar
PMID:Leishmania gp63 molecule implicated in cellular adhesion lacks an Arg-Gly-Asp sequence. 232 59

Heat-inactivated calf-, human-, and especially fetal calf serum stimulate infection of Vero cells by cell culture-derived trypomastigotes of Trypanosoma cruzi: the stimulatory effect is more marked with extracellular activated parasites or trypsinized trypomastigotes than with recently released parasites. The augmented invasion is not the consequence of a stimulation of attachment of trypomastigotes to host cells. Various sialoglycoproteins like fetuin, transferrin, fibrinogen, alpha-1-antitrypsin, mucin and goat-IgG are also effective in enhancing in vitro infectivity. Colominic acid also stimulates invasion, but other non-sialic polyanionic compounds are either ineffective (chondroitin sulfate, poly-aspartic acid) or inhibitory (heparin, phytic acid, myo-inositol hexasulfate). Fetuin, the best stimulatory compound tested, gives half-maximal activation with approximately 0.03 mg ml-1, and total activation with 0.5-1 mg ml-1. The enhancement of infectivity is time-dependent (2-3 h for maximal activation) at 37 degrees C and does not occur at 0 degrees C. Desialidated-fetuin or -fetal calf serum do not stimulate infectivity at all. Treatment with fetuin of parasites alone (or Vero cells alone), followed by removal of free fetuin and by interaction with untreated Vero cells (or parasites) indicates that the stimulation effect of fetuin occurs mainly on the trypomastigotes. No specific binding of [125I]fetuin to the parasites could be demonstrated, and incubation with exogenous neuraminidase of trypomastigotes previously activated by fetuin, reverses nearly completely the stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Biochem Parasitol 1987 Jan 15
PMID:The effect of fetuin and other sialoglycoproteins on the in vitro penetration of Trypanosoma cruzi trypomastigotes into fibroblastic cells. 243 49

Hepatitis B surface antigen possesses the group-specific determinant called a and one or another member from each of two pairs of allelic determinants, d and y as well as w and r, thereby creating the four major subtypes, adw, adr, ayw and ayr. In the sequence of major surface antigen polypeptides made of 226 amino acid residues, lysine or arginine at amino acid position 122 specifies d or y determinant, and lysine or arginine at position 160 specifies w or r determinant, respectively. By means of site-directed mutagenesis and expression of mutant genes in cultured cells, the mechanism for the loss of subtypic determinants on surface antigens was investigated at the molecular level. A rare sample of surface antigen of subtype ad, devoid of w or r determinant, had asparagine at position 160. When it was converted to lysine, the surface antigen of subtype adw was obtained. Two samples of surface antigen were subtyped as ar. They lacked d determinant, despite having lysine at position 122 which usually specified it. They differed from all reported sequences of surface antigen in amino acid 144 or 145. They displayed d determinant when amino acid 144 was converted from glutamic acid to aspartic acid, or when amino acid 145 was changed from alanine to glycine. These results indicate that the key amino acid residue at position 122 or 160 is indispensable for the expression of subtypic determinants and that some distant residues are also crucially involved in conforming them.
Mol Immunol 1989 Feb
PMID:The loss of subtypic determinants in alleles, d/y or w/r, on hepatitis B surface antigen. 246 92

SOD-4, a cytosolic form of superoxide dismutase in maize, originally was defined as a single band of activity by zymogram analysis. The protein was purified to "homogeneity" as shown by a single band on native or denaturing polyacrylamide gels and a single spot on two dimensional gels. The N-terminal amino acid sequence for the first 20 residues was determined for the purified SOD-4 protein. All residues were clearly determined except for residue twelve, where both glutamic and aspartic acids were found. A maize lambda gt11 cDNA library was constructed from scutellar poly(A)+ RNA. Two cDNAs were isolated, restriction mapped, and their DNA sequences determined. The amino acid sequence deduced from both cDNAs matched perfectly the N-terminal sequence of the purified protein except for the residue at position 12. Significantly, at the twelfth codon, one cDNA was found to code for glutamic acid and the other cDNA had a codon for aspartic acid. Both cDNAs contained similar but not identical 5' and 3' untranslated sequences. Both cDNAs contained polyadenylation signals and tails. cDNA isolations, RNA, and genomic DNA blots confirm the existence and expression of two genes that produce indistinguishable SOD-4 proteins.
Mol Gen Genet 1989 Oct
PMID:Two cDNAs encode two nearly identical Cu/Zn superoxide dismutase proteins in maize. 248 36

Muscarinic acetylcholine receptors contain a region encompassing the second and third transmembrane domains that is rich in conserved aspartic acid residues. To investigate the role of four conserved aspartic acids at positions 71, 99, 105, and 122 in muscarinic receptor function, point mutations in the rat m1 muscarinic receptor gene were made that converted each Asp to Asn, and wild type or mutant genes were stably expressed in Chinese hamster ovary cells that normally lack muscarinic receptors. Substitution of Asp71 or Asp122 with Asn produced mutant receptors that displayed high affinity for carbachol but decreased efficacy and potency, respectively, in agonist-induced activation of phosphoinositide hydrolysis, suggesting that these residues may mediate receptor-GTP binding protein interactions. Substitution of Asp99 or Asp105 with Asn produced marked decreases in ligand binding affinities and/or covalent incorporation of [3H] propylbenzilylcholine mustard, suggesting that these residues may be involved in receptor-ligand interactions.
Mol Pharmacol 1989 Dec
PMID:Site-directed mutagenesis of m1 muscarinic acetylcholine receptors: conserved aspartic acids play important roles in receptor function. 255 34

The amino acid sequence, arginine-glycine-aspartic acid (RGD), found in some cell adhesive proteins, is a recognition signal for the receptor protein. It is interesting that we have found the RGD sequence in terminal protein (TP) of bacteriophages phi 29 and M2 near an amino acid, the serine residue at 232, covalently linked to the terminal nucleotide of their DNAs. At the initiation of protein-primed DNA replication, TP is essential for the recognition of replication machinery containing DNA polymerase and primer protein (PP; PP becomes TP upon linking the first nucleotide, and hence the primary structure of TP is the same as that of PP). Synthetic peptide RGD specifically inhibited transfection of phi 29 and M2. The target of the RGD peptide is shown to be TP by marker rescue experiments, suggesting that a receptor for the RGD sequence exists in TP. Furthermore, the peptide inhibited the in vitro protein-priming reaction of DNA replication. We propose that the RGD sequence of PP and a putative receptor on TP is utilized for the molecular recognition initiating DNA replication.
Mol Gen Genet 1989 Dec
PMID:An inhibitory effect of RGD peptide on protein-priming reaction of bacteriophages phi 29 and M2. 260 28

Phosphorylation of the alpha subunit of the eucaryotic translation initiation factor (eIF-2 alpha) by the double-stranded RNA-activated inhibitor (DAI) kinase correlates with inhibition of translation initiation. The importance of eIF-2 alpha phosphorylation in regulating translation was studied by expression of specific mutants of eIF-2 alpha in COS-1 cells. DNA transfection of certain plasmids could activate DAI kinase and result in poor translation of plasmid-derived mRNAs. In these cases, translation of the plasmid-derived mRNAs was improved by the presence of DAI kinase inhibitors or by the presence of a nonphosphorylatable mutant (serine to alanine) of eIF-2 alpha. The improved translation mediated by expression of the nonphosphorylatable eIF-2 alpha mutant was specific to plasmid-derived mRNA and did not affect global mRNA translation. Expression of a serine-to-aspartic acid mutant eIF-2 alpha, created to mimic the phosphorylated serine, inhibited translation of the mRNAs derived from the transfected plasmid. These results substantiate the hypothesis that DAI kinase activation reduces translation initiation through phosphorylation of eIF-2 alpha and reinforce the importance of phosphorylation of eIF-2 alpha as a way to control initiation of translation in intact cells.
Mol Cell Biol 1989 Mar
PMID:The phosphorylation state of eucaryotic initiation factor 2 alters translational efficiency of specific mRNAs. 265 93

The human malarial parasite Plasmodium falciparum secretes a histidine-rich protein (HRP-II) from infected erythrocytes. HRP-II has a very high content of histidine (H) (34%), alanine (A) (37%) and aspartic acid (D) (10%) and many contiguous repeats of the sequences AHH and AHHAAD. The histidine content of the protein suggested the potential to bind metal ions. We have demonstrated by metal chelate chromatography an extraordinary capacity of HRP-II to bind zinc ions (Zn2+) and employed this characteristic to isolate the extracellular protein. The HRP-II was further purified by antibody affinity chromatography. The identity of the purified protein was verified by relative molecular weight on denaturing polyacrylamide gels, by reactivity with monoclonal antibodies and monospecific rabbit antiserum, and by comparison of the amino-acid analysis with that derived from the cloned gene sequence. Analysis of the sequence for periodicities using the hydrophobic moment method indicated that HRP-II may potentially form a 3/10 helix. Immunoprecipitation of HRP-II from culture supernatants of parasites metabolically labeled with tritiated sugars showed that the extracellular form of HRP-II is a glycoprotein containing galactose.
Mol Biochem Parasitol 1989 Jun 15
PMID:Purification and partial characterization of an unusual protein of Plasmodium falciparum: histidine-rich protein II. 267 20

The gene for the A chain of ricin toxin was fused to a beta-galactosidase marker cistron via a DNA sequence encoding a short collagen linker, and the tripartite fusion protein was expressed in Escherichia coli. Site-specific mutagenesis was used to change glutamic acid residue 177 to aspartic acid or alanine. When the mutant proteins were expressed, purified, and tested quantitatively for enzymatic activity, the carboxylate function at position 177 was found not to be absolutely essential for ricin toxin A-chain catalysis.
Mol Cell Biol 1989 Nov
PMID:Role of glutamic acid 177 of the ricin toxin A chain in enzymatic inactivation of ribosomes. 268 71


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