Conferral of allostery to Thermus sp. GH5 methylglyoxal synthase by a single mutation

2012 ◽  
Vol 152 (6) ◽  
pp. 531-538 ◽  
Author(s):  
Z. Farsi ◽  
H. Pein ◽  
M. Pazhang ◽  
S. Zareian ◽  
S.-O. Ranaei-Siadat ◽  
...  
Keyword(s):  
Single Mutation ◽  
Methylglyoxal Synthase

HLA Genotype of Patients with Severe Haemophilia A due to Intron 22 Inversion with and without Inhibitors of Factor VIII

1997 ◽  
Vol 77 (02) ◽  
pp. 238-242 ◽  
Author(s):  
J Oldenburg ◽  
J K Picard ◽  
R Schwaab ◽  
H H Brackmann ◽  
E G D Tuddenham ◽  
...  
Keyword(s):  
Factor Viii ◽  
Major Gene ◽  
Statistical Significance ◽  
Strong Association ◽  
Molecular Genetic ◽  
Single Mutation ◽  
Severe Haemophilia ◽  
Extended Haplotype ◽  
Intron 22 Inversion ◽  
Hla Genotype

SummaryMolecular genetic studies have shown that development of antibodies to factor VIII (inhibitors) occurs most frequently in patients with severe haemophilia due to major gene lesions including inversions, stop codons and large deletions. Previous studies of HLA type were performed on inhibitor and non-inhibitor patients with diverse uncharacterised mutations which may have confounded detection of significant associations. We therefore selected a group of patients with a single mutation type, the prevalent intron 22 inversion, with or without inhibitors, to determine HLA genotype. Seventy-one such patients, 42 without and 29 with inhibitors (13 high, 9 low and 7 transient responders) were genotyped for MHC Class I HLA-A, -B, -C and Class II HLA-DQA, -DQB and -DRB loci. No strong correlation of any HLA-allele to inhibitor or non-inhibitor status was found. However, alleles of the haplotype HLA-A3, HLA-B7, HLA-C7, HLA-DQA0102, HLA-DQB0602, HLA-DR15 occurred more often in inhibitor patients. Since the alleles of this extended haplotype are common in the North European population only a very strong association would achieve statistical significance. Further studies of groups of patients similar to those studied here will be needed to confirm or exclude this association.

scholarly journals Alteration of high and low spin equilibrium by a single mutation of amino acid 209 in mouse cytochromes P450

1991 ◽  
Vol 266 (6) ◽  
pp. 3380-3382
Author(s):  
M Iwasaki ◽  
R Juvonen ◽  
R Lindberg ◽  
M Negishi
Keyword(s):  
Amino Acid ◽  
Cytochromes P450 ◽  
Single Mutation

scholarly journals Context-specific action of macrolide antibiotics on the eukaryotic ribosome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maxim S. Svetlov ◽  
Timm O. Koller ◽  
Sezen Meydan ◽  
Vaishnavi Shankar ◽  
Dorota Klepacki ◽  
...  
Keyword(s):  
Amino Acid Sequences ◽  
Macrolide Antibiotics ◽  
Single Mutation ◽  
Sequence Motifs ◽  
Eukaryotic Translation ◽  
Eukaryotic Ribosome ◽  
Cellular Translation ◽  
Distinct Sequence ◽  
Exit Tunnel ◽  
Context Specific

AbstractMacrolide antibiotics bind in the nascent peptide exit tunnel of the bacterial ribosome and prevent polymerization of specific amino acid sequences, selectively inhibiting translation of a subset of proteins. Because preventing translation of individual proteins could be beneficial for the treatment of human diseases, we asked whether macrolides, if bound to the eukaryotic ribosome, would retain their context- and protein-specific action. By introducing a single mutation in rRNA, we rendered yeast Saccharomyces cerevisiae cells sensitive to macrolides. Cryo-EM structural analysis showed that the macrolide telithromycin binds in the tunnel of the engineered eukaryotic ribosome. Genome-wide analysis of cellular translation and biochemical studies demonstrated that the drug inhibits eukaryotic translation by preferentially stalling ribosomes at distinct sequence motifs. Context-specific action markedly depends on the macrolide structure. Eliminating macrolide-arrest motifs from a protein renders its translation macrolide-tolerant. Our data illuminate the prospects of adapting macrolides for protein-selective translation inhibition in eukaryotic cells.

scholarly journals A single mutation in uncoupling protein of rat brown adipose tissue mitochondria abolishes GDP sensitivity of H+ transport.

1994 ◽  
Vol 269 (10) ◽  
pp. 7435-7438
Author(s):  
D.L. Murdza-Inglis ◽  
M. Modriansky ◽  
H.V. Patel ◽  
G. Woldegiorgis ◽  
K.B. Freeman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Single Mutation ◽  
Brown Adipose

scholarly journals Mitochondrial Syndromes Revisited

2021 ◽  
Vol 10 (6) ◽  
pp. 1249
Author(s):  
Daniele Orsucci ◽  
Elena Caldarazzo Ienco ◽  
Andrea Rossi ◽  
Gabriele Siciliano ◽  
Michelangelo Mancuso
Keyword(s):  
Clinical Trials ◽  
Genetic Basis ◽  
Phenotypic Variability ◽  
Mitochondrial Diseases ◽  
Genetic Alterations ◽  
Mitochondrial Disorders ◽  
Single Mutation ◽  
Multicenter Studies ◽  
Future Studies ◽  
Clinical Syndromes

In the last ten years, the knowledge of the genetic basis of mitochondrial diseases has significantly advanced. However, the vast phenotypic variability linked to mitochondrial disorders and the peculiar characteristics of their genetics make mitochondrial disorders a complex group of disorders. Although specific genetic alterations have been associated with some syndromic presentations, the genotype–phenotype relationship in mitochondrial disorders is complex (a single mutation can cause several clinical syndromes, while different genetic alterations can cause similar phenotypes). This review will revisit the most common syndromic pictures of mitochondrial disorders, from a clinical rather than a molecular perspective. We believe that the new phenotype definitions implemented by recent large multicenter studies, and revised here, may contribute to a more homogeneous patient categorization, which will be useful in future studies on natural history and clinical trials.

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