Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085632 (apathy)
 4,089 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies [G. S. Hudson et al. (1989) J. Biol. Chem. 265, 808-814] showed that the faster turnover rates and lower affinities for CO2 of ribulosebisphosphate carboxylase/oxygenases from C4 plants, compared to C3 and C3/C4 plants, were specified by the chloroplast-encoded large subunits. In pairs of closely related C3 and C4 species from three genera, these kinetic changes were accompanied by only three to six amino acid residue substitutions, depending on the genus. None of these substitutions occurred near the active site and only one, 309Met (C3) to Ile (C4), was common to all three genera. Unlike the plant carboxylases, the highly homologous enzyme from the cyanobacterium Synechococcus PCC 6301 folds and assembles properly when its rbcL and rbcS genes are coexpressed in Escherichia coli. Furthermore, the cyanobacterial enzyme has Ile at position 309 of the large subunit, a high turnover number, and a poor affinity for CO2. 309Ile was replaced with Met and several other residues by site-directed mutagenesis of the cyanobacterial rbcL. Met and Leu were tolerated at this position with no alteration in the kinetic or structural properties of the assembled holoenzyme. However, substitution with Val, Gly, Trp, or Arg prevented the assembly of the subunits. The indifference to Met or Ile at this position, as well as the tolerance for Leu which is not observed with any natural ribulosebisphosphate carboxylase, leads to the conclusion that either the 309Met/Ile substitution has no effect on the kinetic properties of the plant enzyme, despite the correlation apparent in previous studies, or the cyanobacterial enzyme is sufficiently different from the plant enzyme in other respects that the influence of residue 309 is masked.
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PMID:Effects of mutations at residue 309 of the large subunit of ribulosebisphosphate carboxylase from Synechococcus PCC 6301. 144 69

The in-vitro activity of a combination of ranitidine bismuth citrate (RBC) and metronidazole against metronidazole-resistant Helicobacter pylori strains (MIC > or = 8 mg/L) was evaluated by agar dilution chequerboard and killing curve methods. Twenty-five metronidazole-resistant strains were used in the chequerboard method, using Mueller-Hinton agar plus 7% lysed horse blood, an inoculum of 10(6) cfu/spot and incubation in a 10% CO2 atmosphere at 37 degrees C for 3-5 days. Synergy was defined as a fractional inhibitory concentration (FIC) index of < or = 0.5, partial synergy as 0.5 < FIC < or = 1, indifference as 1 < FIC < or = 4 and antagonism as FIC > 4. For nine strains, killing curves were constructed for metronidazole and RBC individually and in combination at 1 x MIC. The number of viable colonies was counted at time 0 and after 2, 4, 6, 8 and 24 h; the combination was defined as synergic if it produced a decrease of > or = 2 log10 cfu/mL compared with the most active single agent. Metronidazole MICs ranged from 8 to 128 mg/L and RBC MICs from 0.125 to 4 mg/L. The minimum FIC ranged from 0.28 to 1 and the maximum FIC from 1 to 1.25. When RBC and metronidazole were combined, all the metronidazole-resistant H. pylori strains revealed partial (68%) or total (32%) synergy. Five out of the nine strains also exhibited synergy at 4, 6 or 8 h incubation when tested by the killing curve method although three other strains exhibited no synergy. In the last strain, a 2log10 decrease in the initial number was observed with RBC alone or combined with metronidazole.
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PMID:Study of the combination of ranitidine bismuth citrate and metronidazole against metronidazole-resistant Helicobacter pylori clinical isolates. 978 70