Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The function of human immunodeficiency virus nef gene product has been much debated but the precise activity of this protein in the HIV replication cycle remains unknown. HIV-1 Nef was obtained as a fusion protein with maltose binding protein (MBF), purified by amylose column chromatography and separated from MBP by cleavage with factor Xa. Purified HIV-1 Nef protein, but not the fusion protein MBP-Nef, binds to RNA in vitro as tested by three different assays, radioactive or non-radioactive. North-western analysis, UV cross-linking or band-shift analysis. This activity was lost in a deletion mutant lacking 22 amino acids from the amino terminus of HIV-1 Nef, while a deletion of 44 residues from the carboxy terminus of the protein does not impair the RNA binding activity. Moreover, a single amino acid replacement, Arg to Gly at position 22 produces a Nef variant deficient in its ability to interact with RNA. Different Nef proteins from HIV-1, HIV-2 or SIV were fused to MBP and cleaved with factor Xa. The different Nef proteins were all endowed with RNA-binding capacity. Sequence similarities between several RNA binding proteins, including picornavirus 2C and different Nef proteins are observed. The function of Nef during the HIV replication cycle is discussed on the basis of the present findings.
 ...
PMID:Human immunodeficiency virus (HIV) Nef is an RNA binding protein in cell-free systems. 887 44

To induce peptide-specific antibodies in mice, as a model for vaccination against human immunodeficiency virus (HIV), lipopeptide analogs conjugated with three repeating units (KAB-112; designated as gp120-peptide) of a part (Gly-Pro-Gly-Arg-Ala-Phe) of the amino acid sequences of the V3 loop region in gp120 of HIV were synthesized. The mitogenicity, production of nitric oxide (NO) and induction of peptide-specific antibodies in mice by synthetic lipopeptides were examined. Compounds, KAB-8 (diacylglycerol-tetrapeptide having a part of the amino acid sequence in Escherichia coli), KAB-116 (diacylglycerol-cysteine), KAB-117 (diacylglycerol with gp120-peptide) and KAB-121 (KAB-8 with gp120-peptide) were capable of increasing significantly the incorporation of [3H]thymidine into splenocytes of C3H/He mice at concentrations ranging from 12.5 to 100 microM, but KAB-112 (gp120-peptide) and KAB-115 (monoacylglycerol with gp120-peptide) did not show such activity. The compounds, KAB-8, KAB-117 and 121, exhibited NO production in murine macrophages. When 50 nmol of these compounds was administered intraperitoneally into BALB/c mice on days 0, 16 and 46, the peptide-specific antibody titers in their sera produced by each compound were determined with ELISA. The sera of KAB-117 and KAB-121, which were obtained on days 14, 30, 42, 57 and 70, had a higher titer than that of KAB-112 and KAB-115, suggesting that the diacylglycerol derivative enhance the production of the peptide-specific antibodies.
 ...
PMID:Antibody-producing effects in mice by synthetic immunoactive lipopeptides with the conjugated amino acid sequence of gp120 in human immunodeficiency virus. 891 95

The gene encoding the proteinase from equine infectious anaemia virus (EIAV) was cloned and expressed in Escherichia coli. The recombinant EIAV proteinase was purified to homogeneity and shown to have the ability to process polyprotein and synthetic peptide substrates of human immunodeficiency virus (HIV) origin with an efficiency that can approach that exhibited by HIV proteinase. EIAV proteinase, however, was not susceptible to inhibition by a wide variety of inhibitors of HIV-1 proteinase, including those which have been licenced as anti-AIDS drugs. In this respect, EIAV proteinase behaves like an extreme case of a drug-resistant mutant of HIV-1 proteinase that has arisen under selective drug pressure. Only one potent inhibitor (HBY-793) of HIV-1 proteinase showed comparable efficiency against the EIAV enzyme; the compounds A-77003 and A-76889, which differ only in their stereochemistry and which are otherwise structurally identical to HBY-793 from residues P2 to P2' [nomenclature of Schechter, I. & Berger, A. (1967) Biochem. Biophys. Res. Commun. 27, 157-162], were not effective inhibitors of EIAV proteinase. Mutant forms of EIAV proteinase (Thr30-->Asp and Ile54-->Gly) were generated and their ability to interact with substrates and inhibitors was characterised. HBY-793 inhibited [Gly54]proteinase as effectively as the wild-type proteinase but was tenfold less potent against [Asp30]proteinase. Data interpretations are presented, based on the structure solved for the complex between HBY-793 and EIAV [Gly54]proteinase [Gustchina A., Kervinen, J., Powell, D. J., Zdanov, A., Kay, J. & Wlodawer, A. (1996) Protein Sci. 5, 1453-1465].
 ...
PMID:Expression, characterisation and mutagenesis of the aspartic proteinase from equine infectious anaemia virus. 891 70

Mutations were introduced into the active site triplet (Asp-Thr-Gly) of one or both subunits of a linked dimer of human immunodeficiency virus type 1 proteinase. Mutation of Thr to Ser in one or both subunits did not alter the activity of the enzyme substantially, whereas its mutation to Asn in one subunit caused a dramatic decrease in catalytic efficiency. Mutation of Gly to Val in one subunit also yielded an enzyme with very low activity. The enzymes containing Thr-->Asn and Gly-->Val mutations in both subunits resulted in inactive enzymes, based on their inability to self-process and on assay with an oligopeptide substrate. The dramatic decrease in enzyme efficiency of the mutants was interpreted using molecular models of the enzymes.
 ...
PMID:Activity of linked HIV-1 proteinase dimers containing mutations in the active site region. 896 52

The three-dimensional solution- and solid-state structures of the human immunodeficiency virus type-1 (HIV-1) matrix protein have been determined recently in our laboratories by NMR and X-ray crystallographic methods (Massiah et al. 1994. J Mol Biol 244:198-223; Hill et al. 1996. Proc Natl Acad Sci USA 93:3099-3104). The matrix protein exists as a monomer in solution at low millimolar protein concentrations, but forms trimers in three different crystal lattices. Although the NMR and X-ray structures are similar, detailed comparisons have revealed an approximately 6 A displacement of a short 3(10) helix (Pro 66-Gly 71) located at the trimer interface. High quality electron density and nuclear Overhauser effect (NOE) data support the integrity of the X-ray and NMR models, respectively. Because matrix apparently associates with the viral membrane as a trimer, displacement of the 3(10) helix may reflect a physiologically relevant conformational change that occurs during virion assembly and disassembly. These findings further suggest that Pro 66 and Gly 71, which bracket the 3(10) helix, serve as "hinges" that allow the 3(10) helix to undergo this structural reorientation.
 ...
PMID:Comparison of the NMR and X-ray structures of the HIV-1 matrix protein: evidence for conformational changes during viral assembly. 897 48

The antiviral activities of two saponins, soyasaponin I and II, isolated from soybean (Glycine max Merrill) were studied in vitro against herpes simplex virus type 1 (HSV-1). Soyasaponin II was more potent than soyasaponin I as shown by reduction of HSV-1 production. Soyasaponin II was also found to inhibit the replication of human cytomegalovirus, influenza virus, and human immunodeficiency virus type 1. The action was not due to inhibition of virus penetration and protein synthesis, but might involve a virucidal effect. When acyclovir and soyasaponin II were evaluated in combination for anti-HSV-1 activity, additive antiviral effects were observed for this virus.
 ...
PMID:Inhibitory activity of soyasaponin II on virus replication in vitro. 914 Feb 20

The peptide sequence Gly-Pro-Gly-Arg-Ala-Phe (GPGRAF) is present in many principal neutralizing determinants (PND) of the human immunodeficiency virus type-1 (HIV-1). It has been shown that peptides from the PND sequence contain a significant beta turn in the conserved Gly-Pro-Gly-Arg sequence. In order to find out whether or not the smaller subunits also contain this turn, we have studied the NMR of a hexapeptide [GPGPRAF, peptide (I)], a heptapeptide Gly-Pro-Gly-Arg-Ala-Phe-Cys [GPGRAFC, peptide (II)] and a dodecapeptide [GPGRAFGPGRAF, peptide (III)], retaining the side chain protecting groups. Although the majority of conformations for these peptides are disordered, there is a considerable propensity of structures with beta turn in the GPGR sequence. While peptide (I) and peptide (III) seem to have both type I and type II beta turn conformations, peptide (II) shows a propensity of only type II beta turn. The nascent structures obtained in these peptides may get stabilized as the receptor binding conformation in the presence of the receptors, thus playing a significant role in vaccine development against HIV.
 ...
PMID:NMR study of the peptide present in the principal neutralizing determinant (PND) of HIV-1 envelope glycoprotein gp120. 917 85

The catalytic properties and sensitivity to different inhibitors have been determined for the reverse transcriptase (RT) of group O human immunodeficiency virus type 1 (HIV-1). The RT-coding region was cloned from a new HIV-1 group O isolate from Spain, expressed in Escherichia coli, and purified by affinity chromatography. This new RT showed 79% amino acid sequence identity with the corresponding enzyme of group M subtype B strain BH10. The two enzymes showed very similar kinetics of RNA-dependent DNA polymerization using homopolymeric template-primers and RNase H specific activity. Inhibitor sensitivity to ddTTP and 3'-azido-2',3'-dideoxythymidine triphosphate (AZTTP) was also similar for both enzymes. However, the two enzymes differed dramatically in their sensitivity to several inhibitors. While the RT of the BH10 isolate was sensitive to nevirapine and loviride (IC50 ranged from 0.16 to 8.2 microM, depending on the substrates used), the enzyme of the Spanish HIV-1 group O isolate showed high-level resistance to those compounds (IC50 > 200 microM). The amino acid sequence of the RT of group O HIV-1 contains three amino acids (Cys-181, Glu-179, and Gly-98), which are found in group M subtype B strains resistant to nonnucleoside RT inhibitors. The recombinant group O HIV-1 RT should be useful for studies aimed at discovering and designing drugs directed toward group O isolates of HIV-1.
 ...
PMID:Characterization of the reverse transcriptase of a human immunodeficiency virus type 1 group O isolate. 932 44

The effects of the human immunodeficiency virus type 1 envelope protein gp120 on the release of GABA elicited by N-methyl-D-aspartate (NMDA) from rat hippocampal neurons in primary culture has been investigated. NMDA (1-300 microM) increased in a concentration-dependent manner (EC50 =37.9+/-12 microM) the release of [3H]-GABA. The effect of 100 microM NMDA was prevented by 30 microM of the GABA transport inhibitor N-(4,4-diphenyl-3-butenyl)guvacine (SKF 100330A). Glycine (10 microM) or gp120 (0.01 microM) affected neither the basal nor the NMDA-evoked [3H]-GABA release. The NMDA (100 microM)-evoked release was prevented by 5,7-dichloro-kynurenic acid (5,7-DCKA), a selective antagonist at the glycine site of the NMDA receptor, in a concentration-dependent manner (IC50 approximately 0.3 microM). Glycine (3-10 microM) or gp120 (0.003-0.01 microM) produced reversal of the 5,7-DCKA antagonism in a way that suggested competition at a same site; gp120 was at least 3 orders of magnitude more potent than glycine. It is suggested that gp120 may mimic glycine at NMDA receptors.
 ...
PMID:Gp120 can revert antagonism at the glycine site of NMDA receptors mediating GABA release from cultured hippocampal neurons. 933 60

The cellular protein, cyclophilin A (CypA), is incorporated into the virion of the type 1 human immunodeficiency virus (HIV-1) via a direct interaction with the capsid domain of the viral Gag polyprotein. We demonstrate that the capsid sequence 87His-Ala-Gly-Pro-Ile-Ala92 (87HAGPIA92) encompasses the primary cyclophilin A binding site and present an X-ray crystal structure of the CypA/HAGPIA complex. In contrast to the cis prolines observed in all previously reported structures of CypA complexed with model peptides, the proline in this peptide, Pro 90, binds the cyclophilin A active site in a trans conformation. We also report the crystal structure of a complex between CypA and the hexapeptide HVGPIA, which also maintains the trans conformation. Comparison with the recently determined structures of CypA in complexes with larger fragments of the HIV-1 capsid protein demonstrates that CypA recognition of these hexapeptides involves contacts with peptide residues Ala(Val) 88, Gly 89, and Pro 90, and is independent of the context of longer sequences.
 ...
PMID:Crystal structure of cyclophilin A complexed with a binding site peptide from the HIV-1 capsid protein. 938 32


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>