Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.5.1.3 (dihydrofolate reductase)
 5,819 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adapting metabolic enzymes of microorganisms to low temperature environments may require a difficult compromise between velocity and affinity. We have investigated catalytic efficiency in a key metabolic enzyme (dihydrofolate reductase) of Moritella profunda sp. nov., a strictly psychrophilic bacterium with a maximal growth rate at 2 degrees C or less. The enzyme is monomeric (Mr=18,291), 55% identical to its Escherichia coli counterpart, and displays Tm and denaturation enthalpy changes much lower than E. coli and Thermotoga maritima homologues. Its stability curve indicates a maximum stability above the temperature range of the organism, and predicts cold denaturation below 0 degrees C. At mesophilic temperatures the apparent Km value for dihydrofolate is 50- to 80-fold higher than for E. coli, Lactobacillus casei, and T. maritima dihydrofolate reductases, whereas the apparent Km value for NADPH, though higher, remains in the same order of magnitude. At 5 degrees C these values are not significantly modified. The enzyme is also much less sensitive than its E. coli counterpart to the inhibitors methotrexate and trimethoprim. The catalytic efficiency (kcat/Km) with respect to dihydrofolate is thus much lower than in the other three bacteria. The higher affinity for NADPH could have been maintained by selection since NADPH assists the release of the product tetrahydrofolate. Dihydrofolate reductase adaptation to low temperature thus appears to have entailed a pronounced trade-off between affinity and catalytic velocity. The kinetic features of this psychrophilic protein suggest that enzyme adaptation to low temperature may be constrained by natural limits to optimization of catalytic efficiency.
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PMID:Moritella cold-active dihydrofolate reductase: are there natural limits to optimization of catalytic efficiency at low temperature? 1294 4

The blackcap (Sylvia atricapilla) is a common Palearctic migratory warbler, and haemosporidian parasites are common in this species. However, genetic and phenotypic diversity of haemosporidians in warblers has been insufficiently investigated and poorly linked. We addressed this issue by combining molecular and microscopy data for detection of pigment-forming haemosporidians of the genera Haemoproteus and Plasmodium. Blood samples from 498 blackcaps were collected at 7 different sites in Europe and investigated for these parasites by polymerase chain reaction (PCR)-based techniques and microscopic examination. In all, 56% of the birds were infected by at least 1 out of 25 distinct mitochondrial cytochrome b (cyt b) gene lineages of these haemosporidians. It is concluded that the blackcap is infected not only with blackcap specific haemosporidians, but also with Haemoproteus majoris, which is a host generalist and common in birds belonging to the Paridae. Haemoproteus pallidulus sp. nov. is described based on morphology of its blood stages and segments of the cyt b and dihydrofolate reductase/thymidylate synthase (DHFR-TS) genes. This study provides evidence that genetic diversity of haemosporidian parasites might be positively correlated with migratory strategies of their avian hosts; it also contributes to the value of both microscopy and molecular diagnostics of avian blood parasites.
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PMID:Molecular phylogenetic and morphological analysis of haemosporidian parasites (Haemosporida) in a naturally infected European songbird, the blackcap Sylvia atricapilla, with description of Haemoproteus pallidulus sp. nov. 1976 50