UMLS:C0021051 - FACTA Search

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)

Benign lymphoepithelial cysts (BLC) are rare disorders of salivary glands (0.6%). In patients infected by HIV, they are seen more often. In comparison to sporadic BLC, the patients are younger, the diameter of the cysts is up to 5 cm and they are often located bilaterally. At the Department of ENT, Head and Neck Surgery of the Ludwig-Maximilians-University, Munich, ten HIV-infected patients (two females) showed lymphoepithelial cysts (six times bilaterally). One of these revealed a metastasis of a small cell neoplasma near the cysts, another patient showed a non-Hodgkin's lymphoma of low grade malignancy (MALT-type), and one patient additionally had bilateral Warthin's tumours. The BLCs were mostly located in the parotid tail. In three cases, the cysts were found on the inferior border of the parotid and once at the submandibular gland. The age ranged from 27 to 71 years (medium 45.7 years). The mode of HIV infection was homosexuality five times, drug abuse twice, heterosexuality once, and blood products once. In two cases, the channel of transmission was unknown. The majority of the patients showed minor HIV illness (CDC II [n = 2]/CDC III [n = 4]); the rest had advanced immunodeficiency (CDC IV [n = 4]). All the cysts were examined by ultrasonography and NMR. According to the clinical findings and the general stage of health, BLCs were either enucleated (n = 8) or a superficial parotidectomy (n = 5) and selective biopsy of lymph nodes (n = 3) suspected to be malignant were performed.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Cystic lymphoepithelial lesions in the head and neck area in HIV-infected patients]. 801 Oct 27

Phospholipid conjugates of 3'-azido-3'-deoxythymidine (AZT) show activity against the human immunodeficiency virus (HIV) in vitro. In a previous report (K.Y. Hostetler, L.M. Stuhmiller, B.H.M. Lenting, H. van den Bosch and D.D. Richman (1991), J. Biol. Chem. 265, 6112-6117) the syntheses and anti-HIV activities of AZT mono- and diphosphate diglyceride have been described. We now report on the synthesis, characterization and biological activity of 3'-azido-3'-deoxythymidine triphosphate distearoylglycerol (AZTTP-DSG). The compound was prepared by the condensation of AZT diphosphate with distearoylphosphatidic acid morpholidate in anhydrous pyridine at room temperature and purified by means of high-performance liquid chromatography using a silica column. Characterization was performed with 31P-NMR and IR analyses and determination of the fatty acid, phosphorus and nucleoside content of the product. AZTTP-DSG inhibited HIV-1 replication in both CEM and HT4-6C cells at a level intermediate in potency between its mono- and diphosphate analogs. The IC50 values of AZTTP-DSG were 0.33 and 0.79 microM in these two cell lines, respectively. In addition, AZTTP-DSG was less toxic to CEM cells in vitro than the other AZT liponucleotides and reduced viable cell numbers in this cell type by 50% at 1000 microM. Initial studies on the metabolism of AZTTP-DSG revealed that both AZT and AZT monophosphate were liberated from the lipid pro-drug by a rat liver mitochondrial enzyme preparation. These phospholipid derivatives of AZT nucleotides represent pro-drugs for the intracellular delivery of phosphorylated antiviral nucleoside analogs.
...
PMID:Synthesis and antiviral activity of 3'-azido-3'-deoxythymidine triphosphate distearoylglycerol: a novel phospholipid conjugate of the anti-HIV agent AZT. 803 92

The Tat protein of human immunodeficiency virus type 1 enhances transcription by binding to a specific RNA element on nascent viral transcripts. Binding is mediated by a 10-amino acid basic domain that is rich in arginines and lysines. Here we report the three-dimensional peptide backbone structure of a biologically active 25-mer peptide that contains the human immunodeficiency virus type 1 Tat basic domain linked to the core regulatory domain of another lentiviral Tat--i.e., that from equine infectious anemia virus. Circular dichroism and two-dimensional proton NMR studies of this hybrid peptide indicate that the Tat basic domain forms a stable alpha-helix, whereas the adjacent regulatory sequence is mostly in extended form. These findings suggest that the tendency to form stable alpha-helices may be a common property of arginine- and lysine-rich RNA-binding domains.
...
PMID:NMR structure of a biologically active peptide containing the RNA-binding domain of human immunodeficiency virus type 1 Tat. 805 89

Base-pair formation between two hairpin loops--a "kissing" complex--is an RNA-folding motif that links two elements of RNA secondary structure. It is also a unique protein recognition site involved in regulation of ColE1 plasmid DNA replication. The trans-activation response element (TAR), a hairpin and bulge at the 5' end of the untranslated leader region of the human immunodeficiency virus 1 mRNA, enhances the transcription of the virus and is necessary for viral replication. Gel electrophoresis and absorbance melting curves indicate that a synthesized RNA hairpin (Tar*-16) with a loop sequence complementary to the TAR loop sequence (CUGGGA) associates specifically with a 16-nucleotide TAR hairpin (Tar-16) to form a stable complex. RNase T1 probing indicates that the three guanines in the Tar-16 loop become inaccessible in the complex. NMR imino proton spectra reveal that 5 base pairs are formed between the two hairpin loops (Tar-16 and Tar*-16); only the adenine at the 3' terminus of the TAR loop does not form a base pair with the 5'-terminal uracil of the complementary loop. A 14-nucleotide hairpin [CCUA(UCCCAG)UAGG] with a loop sequence complementary to the TAR loop is conserved within the gag gene of human immunodeficiency virus 1. A synthesized RNA hairpin corresponding to this conserved sequence also binds to the Tar-16 hairpin with high affinity. It is possible that the same RNA loop-loop interaction occurs during the viral life cycle.
...
PMID:Characterization of a "kissing" hairpin complex derived from the human immunodeficiency virus genome. 807 46

Proteolytic experiments in conjunction with 1H-NMR spectroscopy show that the Nef (negative factor) protein from human immunodeficiency virus type 1 probably consists of two main domains, the N-terminal anchor domain at amino acid positions 2-65 and the C-terminal core domain at positions 66-206. The N-terminal domain is likely to be located at the surface of the protein, while the C-terminal domain has a compactly folded core and is stable in the absence of the anchor domain. It is conceivable that the core domain represents a functional domain of the Nef protein, activated after the removal of the membrane anchor by the human-immunodeficiency-virus protease or cellular proteases. Nef is stable at pH 5-12 and denatures at 317-322 K. The Nef protein remains in its native conformation in dimethyl-sulfoxide/water mixtures up to 35% (by vol.), and in acetonitrile/water up to 14% (by vol.). Nef refolds spontaneously after denaturation with urea or guanidinium hydrochloride. The 1H-NMR parameters and pKa values of five of the nine histidine residues and one of the seven tyrosine residues were determined and were found in four cases to be typical for residues which are not located in the interior of the protein.
...
PMID:Stability and proteolytic domains of Nef protein from human immunodeficiency virus (HIV) type 1. 817 61

The principal neutralizing determinant (PND) of human immunodeficiency virus (HIV) is located inside the third variable loop (designated the V3 loop) of the envelope glycoprotein gp120. The V3 loop is typically 35 amino-acids long, and the 1st and the 35th residues in the loop are invariant cystines involved in a disulfide-bridge. Although PNDs from different HIV isolates contain a conserved GPG-sequence, the amino acids flanking the conserved sequence show hypervariability among HIV isolates; the GPG and the two flanking regions are collectively referred to as the GPG-crest or the PND. The amino acid sequence variability in the GPG-crest gives rise to different antigenic specificities for different PNDs from different HIV isolates. By combining two-dimensional nuclear magnetic resonance (2D NMR) and molecular modeling techniques, we have developed a method to study (1) the global tertiary fold of the V3 loops of HIV and (2) the local structure of the PND at the tip of the V3 loop. In this article, we report the results of our structural studies on the V3 loop of a Thailand HIV isolate. The sequential assignment is made by combining DQF-COSY, TOCSY, and NOESY/ROESY experiments. Various intra- and inter-residue inter-proton distances are estimated by full-matrix analyses of the NOESY data at 100 and 400 ms of mixing times and of the ROESY data at 60 and 200 ms of mixing times. 100 inter-residue distances are used as structural constraints in a simulated annealing procedure to derive energetically stable structures. Two functional motifs in the V3 loop, i.e., the glycosylation site and the GPG-crest, form defined structures: a turn is located at the glycosylation site, and the GPG-crest forms a protruding domain with a type-II GPGQ turn. The other regions of the V3 loop are rather flexible--especially the C-terminal DIRKAYC-stretch. These flexible regions of the V3 loop lead to conformational flexure of the entire V3 loop without altering the local structures of the glycosylation site or the GPG-crest. However, the ROESY experiments revealed no slow exchange among different V3 loop conformations, and therefore the flexible conformations are in fast exchange within the NMR time scale. The extent of this conformational flexibility is also discussed.
...
PMID:Solution structure of the V3 loop of a Thailand HIV isolate. 828 61

The nucleocapsid protein NCp7 of the human immunodeficiency virus type I (HIV-1) is a 72 amino acid peptide containing two zinc fingers of the type CX2CX4HX4C linked by a short basic sequence 29RAPRKKG35. NCp7 was shown to activate in vitro both viral RNA dimerization and replication primer tRNA(Lys,3) annealing to the initiation site of reverse transcription. In order to clarify the possible structural role of the zinc fingers in the various functions of NCp7, complete sequence specific 1H NMR assignment of the entire protein was achieved by two-dimensional NMR experiments. Moreover, to characterize the role of the peptide linker in NCp7 folding, a synthetic analogue with an inversion of Pro31 configuration was studied by NMR and fluorescence techniques. Several long range NOEs implying amino acid protons from the folded zinc fingers and the spacer, such as Ala25 and Trp37, Phe16 and Trp37, Arg32 and Trp37, Lys33 and Trp37, Cys18 and Lys33 disappeared in the D-Pro31 (12-53)NCp7, confirming the spatial proximity of the two CCHC boxes observed in the (13-51)NCp7. This was also confirmed by iodide fluorescence quenching experiments. The N and C-terminal parts of NCp7 displayed a large flexibility except for two short sequences Tyr56 to Gly58 and Tyr64 to Gly66, which seemed to oscillate between random-coil and helical conformations. The biological relevance of the structural characteristics of NCp7 was studied in vitro and in vivo. Substitution of Pro31 by D-Pro31 in the active (13-64)NCp7 peptide led to a severe reduction of dimerization in vitro. Moreover, site-directed mutagenesis substituting Leu for Pro31 resulted in the formation of non-infectious and immature viral particles. These results suggest that the spatial proximity of the zinc fingers induced by the peptide linker, plays a critical role in encapsidation of genomic RNA and morphogenesis of HIV-1 infectious particles.
...
PMID:Conformational behaviour of the active and inactive forms of the nucleocapsid NCp7 of HIV-1 studied by 1H NMR. 828 49

We report comprehensive NMR studies in solution of the human-immunodeficiency-virus (HIV)-1 protease. Stable solutions of the protease were obtained by complexing the protein to a designed cyclic urea inhibitor DMP 323. A variety of triple-resonance experiments provided essentially complete 1H, 13C and 15N NMR signal assignments of the protease. These assignments, together with short-range NOE constraints, coupling constants and hydrogen-exchange data, yielded the secondary structure of the protease in solution. The results reported herein open the way to the determination of the high-resolution three-dimensional solution structures of protease/inhibitor complexes, as well as to studies of protease dynamics and solvent interactions.
...
PMID:Secondary structure and signal assignments of human-immunodeficiency-virus-1 protease complexed to a novel, structure-based inhibitor. 830 36

The nucleic acid interactive properties of a synthetic peptide with sequence of the N-terminal CCHC zinc finger (CCHC = Cys-X2-Cys-X4-His-X4-Cys; X = variable amino acid) of the human immunodeficiency virus (HIV) nucleocapsid protein, Zn(HIV1-F1), have been studied by 1H NMR spectroscopy. Titration of Zn(HIV1-F1) with oligodeoxyribonucleic acids containing different nucleotide sequences reveals, for the first time, sequence-dependent binding that requires the presence of at least one guanosine residue for tight complex formation. The dynamics of complex formation are sensitive to the nature of the residues adjacent to guanosine, with residues on the 3' side of guanosine having the largest influence. An oligodeoxyribonucleotide with sequence corresponding to a portion of the HIV-1 psi-packaging signal, d(ACGCC), forms a relatively tight complex with Zn(HIV1-F1) (Kd = 5 x 10(-6) M). Two-dimensional nuclear Overhauser effect (NOESY) data indicate that the bound nucleic acid exists predominantly in a single-stranded, A-helical conformation, and the presence of more than a dozen intermolecular NOE cross peaks enabled three-dimensional modeling of the complex. The nucleic acid binds within a hydrophobic cleft on the peptide surface. This hydrophobic cleft is defined by the side chains of residues Val1, Phe4, Ile12, and Ala13. Backbone amide protons of Phe4 and Ala13 and the backbone carbonyl oxygen of Lys2 that lie within this cleft appear to form hydrogen bonds with the guanosine O6 and N1H atoms, respectively. In addition, the positively charged side chain of Arg14 is ideally positioned for electrostatic interactions with the phosphodiester backbone of the nucleic acid. The structural findings provide a rationalization for the general conservation of these hydrophobic and basic residues in CCHC zinc fingers, and are consistent with site-directed mutagenesis results that implicate these residues as direct participants in viral genome recognition.
...
PMID:Zinc- and sequence-dependent binding to nucleic acids by the N-terminal zinc finger of the HIV-1 nucleocapsid protein: NMR structure of the complex with the Psi-site analog, dACGCC. 844 88

A point mutation (Ala-589 to Thr) in the transmembrane protein of the human immunodeficiency virus type 1 (HIV-1) has been shown to decrease the sensitivity of the virus to the neutralizing effect of human HIV-1 specific antibodies [(1990) J. Virol. 64, 3240-3248]. Here 17-residue peptides with the parental and mutant sequences were compared: the parental peptide bound antibodies of sera from HIV-1 infected persons more frequently and with higher affinity than the mutant peptide. However, according to circular dichroism (CD), NMR spectroscopy and molecular modelling the peptides have indistinguishable backbone conformations under a variety of experimental conditions. These techniques showed for both peptides that no ordered helix was present in water solution. However, for both peptides in alcohol-water solutions approximately 60% alpha-helix could be induced. The three-dimensional structures of these peptides provide a basis for understanding how this mutation in the transmembrane protein may affect the interaction with both the outer envelope glycoprotein and with antibodies.
...
PMID:Three-dimensional structure and antigenicity of transmembrane-protein peptides of the human immunodeficiency virus type 1. Effects of a neutralization-escape substitution. 849 50

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