scholarly journals Genomic and Evolutionary Insights into Genes Encoding Proteins with Single Amino Acid Repeats

2006 ◽  
Vol 23 (7) ◽  
pp. 1357-1369 ◽  
Author(s):  
Pratibha Siwach ◽  
Saurabh Dilip Pophaly ◽  
Subramaniam Ganesh
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Amino Acid Repeats ◽  
Genes Encoding

scholarly journals Genome-wide evidence for selection acting on single amino acid repeats

2010 ◽  
Vol 20 (6) ◽  
pp. 755-760 ◽  
Author(s):  
W. Haerty ◽  
G. B. Golding
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Amino Acid Repeats ◽  
Genome Wide

scholarly journals Antigen binding and idiotype analysis of antibodies obtained after electroporation of heavy and light chain genes encoding phosphocholine-specific antibodies: a model for T15-idiotype dominance.

1992 ◽  
Vol 176 (6) ◽  
pp. 1637-1643 ◽  
Author(s):  
J J Kenny ◽  
C M Moratz ◽  
G Guelde ◽  
C D O'Connell ◽  
J George ◽  
...  
Keyword(s):  
Immune Response ◽  
Amino Acid ◽  
B Cell ◽  
Molecular Model ◽  
Immunoglobulin M ◽  
Single Amino Acid ◽  
Primary Immune Response ◽  
Antigen Binding ◽  
Large Numbers ◽  
Genes Encoding

Antibodies bearing the T15 idiotype dominate the murine primary immune response to phosphocholine (PC). Analysis of antigen binding of antibodies derived from V1:DFL16.1:JH1 (VH1) germline and N region-derived variant heavy (H) chains and kappa 22, kappa 24, and kappa 8 light (L) chains demonstrates that the T15H:kappa 22L (T15) antibody binds PC at least 20-40 times better than other antibodies derived from alternate germline forms of the VH1 H chain and kappa 22, kappa 24, or kappa 8 L chains. To achieve affinities in the same range as the T15 antibody, kappa 24 and kappa 8 L chain-containing antibodies must have H chains derived from variant N region or somatically mutated VH1 genes. Single amino acid differences at the VD junction of the various germline and N region variant VH1 H chains dictate the L chain that can associate with the H chain to produce a PC-specific antibody. Several H:L combinations give rise to T15 or M167 idiotype-positive antibodies that lack specificity for PC, and single amino acid substitutions or insertions at the VH1:D junction result in the loss of T15 or M167 idiotopes. Based on these observations, our data support a molecular model involving both preferential gene rearrangement and antigen-driven B cell selection to explain T15 idiotype dominance in the immune response to PC. In the absence of N region diversification, large numbers of neonatal B cells bearing the T15H:kappa 22L surface immunoglobulin M (sIgM) receptors would be selected and expanded by autologous or environmental PC antigen into the long-lived peripheral B cell pool.

scholarly journals Multiple Mutations Lead to MexXY-OprM-Dependent Aminoglycoside Resistance in Clinical Strains of Pseudomonas aeruginosa

2013 ◽  
Vol 58 (1) ◽  
pp. 221-228 ◽  
Author(s):  
Sophie Guénard ◽  
Cédric Muller ◽  
Laura Monlezun ◽  
Philippe Benas ◽  
Isabelle Broutin ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Amino Acid ◽  
Multidrug Resistant ◽  
Single Amino Acid ◽  
Leader Peptide ◽  
Dimerization Domain ◽  
Aminoglycoside Resistance ◽  
Content Type ◽  
Clinical Strains ◽  
Genes Encoding

ABSTRACTConstitutive overproduction of the pump MexXY-OprM is recognized as a major cause of resistance to aminoglycosides, fluoroquinolones, and zwitterionic cephalosporins inPseudomonas aeruginosa. In this study, 57 clonally unrelated strains recovered from non-cystic fibrosis patients were analyzed to characterize the mutations resulting in upregulation of themexXYoperon. Forty-four (77.2%) of the strains, classified asagrZmutants were found to harbor mutations inactivating the local repressor gene (mexZ) of themexXYoperon (n= 33; 57.9%) or introducing amino acid substitutions in its product, MexZ (n= 11; 19.3%). These sequence variations, which mapped in the dimerization domain, the DNA binding domain, or the rest of the MexZ structure, mostly affected amino acid positions conserved in TetR-like regulators. The 13 remaining MexXY-OprM strains (22.8%) contained intactmexZgenes encoding wild-type MexZ proteins. Eight (14.0%) of these isolates, classified asagrW1mutants, overexpressed the gene PA5471, which codes for the MexZ antirepressor AmrZ, with 5 strains exhibiting growth defects at 37°C and 44°C, consistent with mutations impairing ribosome activity. Interestingly, oneagrW1mutant appeared to harbor a 7-bp deletion in the coding sequence of the leader peptide, PA5471.1, involved in ribosome-dependent, translational attenuation of PA5471 expression. Finally, DNA sequencing and complementation experiments revealed that 5 (8.8%) strains, classified asagrW2mutants, harbored single amino acid variations in the sensor histidine kinase of ParRS, a two-component system known to positively controlmexXYexpression. Collectively, these results demonstrate that clinical strains ofP. aeruginosaexploit different regulatory circuitries to mutationally overproduce the MexXY-OprM pump and become multidrug resistant, which accounts for the high prevalence of MexXY-OprM mutants in the clinical setting.

scholarly journals Structural features of single amino acid repeats in proteins

FEBS Letters ◽  
1999 ◽  
Vol 448 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Juan A Subirana ◽  
Jaume Palau
Keyword(s):  
Amino Acid ◽  
Structural Features ◽  
Single Amino Acid ◽  
Amino Acid Repeats

scholarly journals Temporal analysis of general control of amino acid biosynthesis in Saccharomyces cerevisiae: role of positive regulatory genes in initiation and maintenance of mRNA derepression.

1984 ◽  
Vol 4 (3) ◽  
pp. 520-528 ◽  
Author(s):  
M D Penn ◽  
G Thireos ◽  
H Greer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Steady State ◽  
Amino Acid ◽  
Gene Product ◽  
Temporal Analysis ◽  
Regulatory Genes ◽  
Single Amino Acid ◽  
Mrna Levels ◽  
Initiation Phase ◽  
Genes Encoding

In Saccharomyces cerevisiae, starvation for a single amino acid results in the derepression of enzyme activities in multiple amino acid biosynthetic pathways. Derepression is a consequence of increased transcription of the genes encoding these enzymes. Analysis of the kinetics of mRNA elevation established that derepression occurs within 5 min of a shift of the culture from rich medium to starvation medium. Any starvation condition was sufficient to trigger an initial high mRNA elevation; however, it was the severity of starvation which determined the steady-state mRNA levels that were subsequently established. The products of the positive regulatory genes AAS101, AAS103, and AAS2 were shown to be required in the initiation phase of this response, whereas the AAS102 gene product was required to maintain the new elevated steady-state mRNA levels. The AAS101 and AAS102 genes were cloned. Consistent with their respective roles in initiation and maintenance of derepression. AAS101 mRNA was found to be expressed at high levels in both rich and starvation media, whereas AAS102 mRNA was derepressed only under starvation conditions. The derepression of AAS102 mRNA is dependent on the AAS101 gene product.

Temporal analysis of general control of amino acid biosynthesis in Saccharomyces cerevisiae: role of positive regulatory genes in initiation and maintenance of mRNA derepression

1984 ◽  
Vol 4 (3) ◽  
pp. 520-528
Author(s):  
M D Penn ◽  
G Thireos ◽  
H Greer
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Steady State ◽  
Amino Acid ◽  
Gene Product ◽  
Temporal Analysis ◽  
Regulatory Genes ◽  
Single Amino Acid ◽  
Mrna Levels ◽  
Initiation Phase ◽  
Genes Encoding

In Saccharomyces cerevisiae, starvation for a single amino acid results in the derepression of enzyme activities in multiple amino acid biosynthetic pathways. Derepression is a consequence of increased transcription of the genes encoding these enzymes. Analysis of the kinetics of mRNA elevation established that derepression occurs within 5 min of a shift of the culture from rich medium to starvation medium. Any starvation condition was sufficient to trigger an initial high mRNA elevation; however, it was the severity of starvation which determined the steady-state mRNA levels that were subsequently established. The products of the positive regulatory genes AAS101, AAS103, and AAS2 were shown to be required in the initiation phase of this response, whereas the AAS102 gene product was required to maintain the new elevated steady-state mRNA levels. The AAS101 and AAS102 genes were cloned. Consistent with their respective roles in initiation and maintenance of derepression. AAS101 mRNA was found to be expressed at high levels in both rich and starvation media, whereas AAS102 mRNA was derepressed only under starvation conditions. The derepression of AAS102 mRNA is dependent on the AAS101 gene product.

scholarly journals 698. Nacubactam Inhibits Class A β-lactamases

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S251-S252
Author(s):  
Melissa D Barnes ◽  
Caryn E Good ◽  
Saralee Bajaksouzian ◽  
Magdalena A Taracila ◽  
David Van Duin ◽  
...  
Keyword(s):  
Amino Acid ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
E Coli ◽  
Class A ◽  
Cell Extracts ◽  
Fixed Concentration ◽  
Genes Encoding ◽  
Inactivation Mechanism ◽  
Research Grant

Abstract Background Nacubactam, formerly RG6080 and OP0595 (Figure 1A), is a bridged diazabicyclooctane (DBO) that inactivates class A and class C β-lactamases. Unlike avibactam, the DBO that is approved for use in combination with ceftazidime, nacubactam also inhibits penicillin binding proteins (i.e., PBP2) in Enterobacteriaceae. We set out to determine the effectiveness of meropenem-nacubactam against Klebsiella pneumoniae clinical strains and to elucidate the structure–function relationships. Methods Minimal inhibitory concentration (MIC) measurements using broth microdilution according to Clinical and Laboratory Standards Institute for meropenem (MERO) ± nacubactam (fixed concentration of 4 mg/L or fixed 1:1 ratio) was performed on 50 clinical K. pneumoniae strains (6 having OXA-48-like β-lactamases and 44 harboring KPC-2 or KPC-3) and 47 isogenic Escherichia coli strains harboring bla genes encoding K. pneumoniae carbapenemase (KPC) variants with single amino acid substitutions in residues that are involved in catalysis. IC50s for selected KPC-2 variants were determined on periplasmic extracts with varying concentrations of nacubactam using nitrocefin as a reporter substrate. Results The MERO combinations with either 4 mg/L or a 1:1 ratio of nacubactam effectively lowered the MERO MICs of K. pneumoniae strains (Figure 1B). Similarly, all E. coli strains expressing blaKPC-2 variants were susceptible to the MERO-nacubactam combinations based on the breakpoint of MERO. The strains harboring K73R, S130G, and K234R had slightly elevated MERO-nacubactam MICs relative to wild type but did not have corresponding increases in MERO MICs. Strains with pBC SK-KPC2, K73R or S130G had 0.015 mg/L MERO MICs. The pBR322-K234R strain had a twofold lower MERO MIC than pBR322-KPC-2 (Figure 1C). The IC50 of cell extracts containing the K234R variant is 781 µM, which is 12-fold higher than that for KPC-2 (66 µM) (Figure 1C). Extracts containing the S130G variant were not inhibited by nacubactam (IC50 > 2.6 mM). Conclusion Meropenem-nacubactam is an effective β-lactam β-lactamase inhibitor combination for Enterobacteriaceae with KPC or OXA-48 β-lactamases. The single amino acid substitutions K73R, S130G, and K234R in KPC-2 affect the inactivation mechanism. Disclosures M. R. Jacobs, F. Hoffmann-La Roche Ltd.: Grant Investigator, Research grant. K. M. Papp-Wallace, F. Hoffmann-La Roche Ltd.: Grant Investigator, Research grant. R. A. Bonomo, F. Hoffmann-La Roche Ltd.: Grant Investigator, Research grant.

scholarly journals Diverse single-amino-acid repeat profiles in the genus Cryptosporidium

Parasitology ◽  
2018 ◽  
Vol 145 (9) ◽  
pp. 1151-1160 ◽  
Author(s):  
Giovanni Widmer
Keyword(s):  
Amino Acid ◽  
Selective Pressure ◽  
Global Analysis ◽  
Single Amino Acid ◽  
Striking Difference ◽  
Cryptosporidium Hominis ◽  
Amino Acid Repeats ◽  
Regulatory Functions ◽  
Simple Sequence ◽  
Cryptosporidium Baileyi

AbstractGenome sequencing has greatly contributed to our understanding of parasitic protozoa. This is particularly the case for Cryptosporidium species (phylum Apicomplexa) which are difficult to propagate. Because of their polymorphic nature, simple sequence repeats have been used extensively as genotypic markers to differentiate between isolates, but no global analysis of amino acid repeats in Cryptosporidium genomes has been reported. Taking advantage of several newly sequenced Cryptosporidium genomes, a comparative analysis of single-amino-acid repeats (SAARs) in seven species was undertaken. This analysis revealed a striking difference between the SAAR profile of the gastric and intestinal species which infect mammals and one species which infects birds. In average, total SAAR length in gastric species is only 25% of the cumulative SAAR length in the genome of Cryptosporidium parvum, Cryptosporidium hominis and Cryptosporidium meleagridis, species infectious to humans. The SAAR profile in the avian parasite Cryptosporidium baileyi stands out due to the presence of long asparagine repeats. Cryptosporidium baileyi proteins with repeats ⩾20 residues are significantly enriched in regulatory functions. As postulated for the related apicomplexan species Plasmodium falciparum, these observations suggest that Cryptosporidium SAARs evolve in response to selective pressure. The putative selective mechanisms driving SAAR evolution in Cryptosporidium species are unknown.

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