Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High-performance liquid chromatography (HPLC) is used to detect testosterone (T)-sensitive peptides in spleen cells isolated from female C57BL/10 mice immunosuppressed against Plasmodium chabaudi malaria by T treatment. Two peaks with retention times of about 25 min and 34 min, respectively, were identified to be diminished by about 52% and 47%, respectively, in spleen cells from T-treated mice compared to those from untreated mice. Amino acid sequencing revealed that the 24 min peak consisted of the dipeptide Met-Phe and the 34 min peak contained a degradative fragment of the alpha-chain of hemoglobin. Our data suggest that the immunosuppressive T treatment of B10 mice induces a perturbation of erythrophagocytosis in spleens.
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PMID:Testosterone-induced diminution of two peptides in spleen cells from testosterone-immunosuppressed B10 mice. 163 11

The alpha-thalassemias (particularly in Asia) can be considered as a three-allele system, with one "normal" allele (N) consisting of a pair of closely linked alpha-chain loci, a second "single" allele (S) in which one of the loci has been lost by deletion, and a third "double" allele (D) in which both have been lost. Representatives of all the sets of fitnesses leading to the maintenance of this condition by selection for malaria resistance have been explored, and after the discarding of unlikely sets of fitnesses, it is found that there will be three outcomes: (1) the S chromosome is fixed, (2) the S and N chromosomes form a stable polymorphism, and (3) the N and D chromosomes form a stable polymorphism, but this can be lost and the population forced to fixation by the introduction of sufficiently large number of S chromosomes. Some Melanesian populations appear to have reached outcome (1), while frequencies in African, Mediterranean, and Middle Eastern populations are not incompatible with outcome (2). Southeast Asian populations, however, which carry S and D chromosomes in high frequency, may be in a state of flux. The D chromosome may form a polymorphism with N locally, but it can be driven from the local population by the introduction of large numbers of S chromosomes. The D chromosome would thus be somewhat analogous to a fugitive species, which can only exist in certain transient environments and is displaced as the environment changes. The possibility that N, S, and D are coexisting as a stable polymorphism can almost certainly be ruled out by a consideration of fitness sets required.
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PMID:Is the doubly deleted alpha-thalassemia gene a "fugitive" allele? 721 38

Malaria remains a human disease of global significance and a major cause of high infant mortality in endemic nations. Parasites of the genus Plasmodium cause the disease by degrading human hemoglobin as a source of amino acids for their growth and maturation. Hemoglobin degradation is initiated by aspartic proteases, termed plasmepsins, with a cleavage at the alpha-chain between residues Phe33 and Leu34. Plasmepsin II is one of the four catalytically active plasmepsins that has been identified in the food vacuole of Plasmodium falciparum. Novel crystal structures of uncomplexed plasmepsin II as well as the complex with a potent inhibitor have been refined with data extending to resolution limits of 1.9A and 2.7A, and to R factors of 17% and 18%, respectively. The inhibitor, N-(3-[(2-benzo[1,3]dioxol-5-yl-ethyl)[3-(1-methyl-3-oxo-1,3-dihydro-isoindol-2-yl)-propionyl]-amino]-1-benzyl-2-(hydroxypropyl)-4-benzyloxy-3,5-dimethoxy-benzamide, belongs to a family of potent non-peptidic inhibitors that have large P1' groups. Such inhibitors could not be modeled into the binding cavity of the structure of plasmepsin II in complex with pepstatin A. Our structures reveal that the binding cavities of the new complex and uncomplexed plasmepsin II are considerably more open than that of the pepstatin A complex, allowing for larger heterocyclic groups in the P1', P2' and P2 positions. Both complexed and uncomplexed plasmepsin II crystallized in space group P2, with one monomer in the asymmetric unit. The structures show extensive interlocking of monomers around the crystallographic axis of symmetry, with areas in excess of 2300A(2) buried at the interface, and a loop of one monomer interacting with the binding cavity of the 2-fold related monomer. Electron density for this loop is only fully ordered in the complexed structure.
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PMID:Novel uncomplexed and complexed structures of plasmepsin II, an aspartic protease from Plasmodium falciparum. 1261 16

The emergence and worldwide spreading of Plasmodium falciparum strains that shown to be resistant to traditional drugs is considered a very serious health problem, given the high mortality and morbidity rate of Malaria. In the search for new drugs against this parasite, Hb hydrolyzing enzymes, such as Plasmepsin II (Plm II), have been classified as very promising targets for therapeutic attacks. In this work, it is developed a cheap and high-throughput heterogeneous enzymatic assay for measuring Plasmepsin II activity in order to use it as a tool in the discovery of new inhibitors of this enzyme. In this assay, Plasmepsin II acts upon a solid-phase bound synthetic peptide (DU2) whose sequence comprises the cleavage site F(33)-L(34) present in Hb alpha-chain. The peptide surface density is quantified by means of a classical ELISA-based procedure. In order to estimate the kinetic constants of the system and to quantify both, enzymatic and inhibitory activity, it was used a model for the kinetics of enzyme quasi-saturable systems previously developed by our group, that fitted very well to the experimental data. It was used Pepstatin as a model inhibitor of Plasmepsin II and the resulting dose-response relation agreed with the expected behavior for the Pepstatin-Plasmepsin II pair under the employed experimental conditions.
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PMID:A heterogeneous enzymatic assay for quantification of Plasmepsin II activity and the evaluation of its inhibitors. 1501 62