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

Mycoplasma fermentans and Mycoplasma pirum have been recovered from human immunodeficiency virus (HIV)-positive persons. M. fermentans has been isolated with much higher frequency from HIV-positive than from HIV-negative persons. Mycoplasma genitalium has been detected by polymerase chain reaction in the blood of a patient with AIDS. Little is known about the biology of these mycoplasmas, especially their physiology, biochemistry, and growth response to inhibitors of essential metabolic loci or transport. Metabolically, they resemble other Mycoplasma species. Those studied lack cytochromes, the tricarboxylic acid cycle, and portions of the hexose monophosphate shunt. According to limited data, they fix CO2, use ATP to phosphorylate fructose-6-phosphate, have substrate phosphorylation and transaminase(s), and interconvert most purines and pyrimidines. The synthesis of thymidine may be limited. They may require a variety of essential small molecules for optimal growth (e.g., pyridoxal phosphate, ribose-1-phosphate). Their pathogenic potential and cultural lability may involve the production of the superoxide anion and the hydroxyl radical. We hypothesize that the mycoplasmas generate toxic oxygenated products that damage the host cell, probably membrane, permitting the mycoplasmas to gain easier access to the interior of the cell. The mycoplasma-damaged host cell membrane may also effect the maturation or release of HIV particles from the cell.
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PMID:The metabolism of AIDS-associated mycoplasmas. 839 28

We extended our previous study with 3'-azido-3'-deoxythymidine nucleotides [Proc. Natl. Acad. Sci. USA 91:5771-5775 (1994)] and examined the effects on human immunodeficiency virus type 1 (HIV-1) integrase of the nucleotides of three nucleoside analogues currently under evaluation in clinical trials: beta-D-2',3'-didehydro-3'-deoxythymidine, beta-D-2'-ara-fluoro-2', 3'-dideoxyadenosine, and beta-L-2',3'-dideoxy-3'-thiacytidine. Beta-D-2',3'-Didehydro-3'-deoxythymidine and beta-D-2'-ara-fluoro-2',3'-dideoxyadenosine nucleotides had IC50 values for strand transfer of 100 and 200 microM, respectively, whereas the corresponding 2',3'-dideoxynucleoside triphosphates, ddT triphosphate and ddA triphosphate, did not inhibit the integrase at 800 and 200 microM, respectively. Beta-L-2',3'-Dideoxy-3'-thiacytidine triphosphate had no effect up to 500 microM. The L-enantiomers of 5-fluoro-2',3'-dideoxycytidine monophosphate and triphosphate had IC50 values of approximately 40 microM, whereas their D-enantiomer isomers showed no inhibition at 200 microM. NAD, pyridoxal phosphate, and coumermycin A1, which exhibit no antiviral activity but are typically used to probe nucleotide binding sites, were also tested. NAD was inactive, and its etheno derivative exhibited activity at 1 mM. In contrast, pyridoxal phosphate (IC50 = 18 microM and coumermycin A1 (IC50 = 5 microM were potent inhibitors. None of the coumermycin monomeric derivatives were active integrase inhibitors. The physiological ribonucleotides ATP and GTP inhibited HIV-1 integrase at or near cellular concentrations, suggesting that they may regulate HIV-1 integrase activity in cells. In general, the active nucleotides tested inhibited binding of HIV-1 integrase to its substrate DNA an inhibited an integrase deletion mutant containing only amino acids 50-212, indicating that nucleotides bind to the enzyme catalytic core. Consisently, the choice of nucleophile in the 3'-processing reaction was blocked to the same extent regardless of the nucleotide used (water, glycerol, or the viral DNA hydroxyl) by the enzyme. These observations suggest new strategies for antiviral drug development that could be based on nucleotide analogues as inhibitors of HIV-1 integrase.
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PMID:Effects of nucleotide analogues on human immunodeficiency virus type 1 integrase. 860 89