scholarly journals A New Evolutionary Variant of the Streptogramin A Resistance Protein, Vga(A)LC, from Staphylococcus haemolyticus with Shifted Substrate Specificity towards Lincosamides

2006 ◽  
Vol 50 (12) ◽  
pp. 4070-4076 ◽  
Author(s):  
G. Novotna ◽  
J. Janata
Keyword(s):  
Amino Acid ◽  
Substrate Specificity ◽  
Resistance Gene ◽  
Atp Binding ◽  
Amino Acid Substitutions ◽  
Abc Proteins ◽  
Susceptible Host ◽  
Staphylococcus Haemolyticus ◽  
New Variant ◽  
Transport Experiment

ABSTRACT We found a new variant of the streptogramin A resistance gene, vga(A)LC, in clinical isolates of Staphylococcus haemolyticus resistant to lincomycin and clindamycin but susceptible to erythromycin and in which no relevant lincosamide resistance gene was detected. The gene vga(A)LC, differing from the gene vga(A) at the protein level by seven amino acid substitutions, was present exclusively in S. haemolyticus strains resistant to both lincosamides and streptogramin A (LSA phenotype). Antibiotic resistance profiles of the ATP-binding cassette (ABC) proteins Vga(A)LC and Vga(A) in the antibiotic-susceptible host S. aureus RN4220 were compared. It was shown that Vga(A)LC conferred resistance to both lincosamides and streptogramin A, while Vga(A) conferred significant resistance to streptogramin A only. Detailed analysis of the seven amino acid substitutions, distinguishing the two related ABC proteins with different substrate specificities, identified the substrate-recognizing site: four clustered substitutions (L212S, G219V, A220T, and G226S) in the spacer between the two ATP-binding cassettes altered the substrate specificity and constituted the lincosamide-streptogramin A resistance phenotype. A transport experiment with radiolabeled lincomycin demonstrated that the mechanism of lincosamide resistance in S. haemolyticus was identical to that of the reported macrolide-streptogramin B resistance conferred by Msr(A).

scholarly journals S-Acylation of Proteins of Coronavirus and Influenza Virus: Conservation of Acylation Sites in Animal Viruses and DHHC Acyltransferases in Their Animal Reservoirs

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 669
Author(s):  
Dina A. Abdulrahman ◽  
Xiaorong Meng ◽  
Michael Veit
Keyword(s):  
Influenza Virus ◽  
Amino Acid ◽  
Ion Channels ◽  
Substrate Specificity ◽  
Influenza A ◽  
3D Structure ◽  
Viral Fitness ◽  
Amino Acid Substitutions ◽  
Essential Function ◽  
Animal Reservoirs

Recent pandemics of zoonotic origin were caused by members of coronavirus (CoV) and influenza A (Flu A) viruses. Their glycoproteins (S in CoV, HA in Flu A) and ion channels (E in CoV, M2 in Flu A) are S-acylated. We show that viruses of all genera and from all hosts contain clusters of acylated cysteines in HA, S and E, consistent with the essential function of the modification. In contrast, some Flu viruses lost the acylated cysteine in M2 during evolution, suggesting that it does not affect viral fitness. Members of the DHHC family catalyze palmitoylation. Twenty-three DHHCs exist in humans, but the number varies between vertebrates. SARS-CoV-2 and Flu A proteins are acylated by an overlapping set of DHHCs in human cells. We show that these DHHC genes also exist in other virus hosts. Localization of amino acid substitutions in the 3D structure of DHHCs provided no evidence that their activity or substrate specificity is disturbed. We speculate that newly emerged CoVs or Flu viruses also depend on S-acylation for replication and will use the human DHHCs for that purpose. This feature makes these DHHCs attractive targets for pan-antiviral drugs.

scholarly journals Effect of Amino Acid Substitutions in the Rad50 ATP Binding Domain on DNA Double Strand Break Repair in Yeast

2004 ◽  
Vol 280 (4) ◽  
pp. 2620-2627 ◽  
Author(s):  
Ling Chen ◽  
Kelly M. Trujillo ◽  
Stephen Van Komen ◽  
Dong Hyun Roh ◽  
Lumir Krejci ◽  
...  
Keyword(s):  
Amino Acid ◽  
Strand Break ◽  
Double Strand Break ◽  
Binding Domain ◽  
Double Strand Break Repair ◽  
Atp Binding ◽  
Amino Acid Substitutions ◽  
Dna Double Strand Break ◽  
Break Repair

scholarly journals Characterization of Chromosome-Mediated BlaOXA-894 in Shewanella xiamenensis Isolated from Pig Wastewater

2019 ◽  
Vol 16 (19) ◽  
pp. 3768
Author(s):  
Huiyun Zou ◽  
Ziyu Zhou ◽  
Huiyu Xia ◽  
Qian Zhao ◽  
Xuewen Li
Keyword(s):  
Amino Acid ◽  
Rural China ◽  
Water Environment ◽  
Amino Acid Substitutions ◽  
Gene Encoding ◽  
Potential Health ◽  
Carbapenem Resistant ◽  
Gene Environment ◽  
New Variant ◽  
Its Gene

A new variant of the blaOXA-546 gene, namely blaOXA-894, was identified on the chromosome of Shewanella xiamenensis isolated from pig wastewater in rural China. OXA-894 differs from OXA-546 (A46V, I219del) and OXA-48 (T167I, I219del) with two amino acid substitutions, respectively. The isolate was resistant to ampicillin, aztreonam, imipenem, meropenem and fosfomycin. Carba NP test confirmed S. xiamenensis strain sx20 as a carbapenemase-producer. The blaOXA-894 gene was located between the gene encoding a LysR family transcriptional regulator and the C15 gene. Its gene environment was similar to other S. xiamenensis with chromosome-located blaOXA-48-like genes. The T24H and T94V amino acid substitutions of LuxS protein were predicted to be deleterious, which may affect the virulence phenotype. The occurrence and potential health risk of carbapenem-resistant S. xiamenensis in a water environment is of concern.

Amino acid substitutions in the first transmembrane domain (TM1) of P-glycoprotein that alter substrate specificity

FEBS Letters ◽  
1997 ◽  
Vol 413 (1) ◽  
pp. 142-146 ◽  
Author(s):  
Yoshitomo Taguchi ◽  
Masaki Morishima ◽  
Tohru Komano ◽  
Kazumitsu Ueda
Keyword(s):  
Amino Acid ◽  
Substrate Specificity ◽  
Transmembrane Domain ◽  
Amino Acid Substitutions ◽  
P Glycoprotein

scholarly journals Roles of Amino Acids 161 to 179 in the PSE-4 Ω Loop in Substrate Specificity and in Resistance to Ceftazidime

1998 ◽  
Vol 42 (10) ◽  
pp. 2576-2583 ◽  
Author(s):  
Christian Therrien ◽  
Francois Sanschagrin ◽  
Timothy Palzkill ◽  
Roger C. Levesque
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Substrate Specificity ◽  
High Activity ◽  
Amino Acid Substitutions ◽  
Hydrolyzing Enzymes ◽  
Hydrolysis Of

ABSTRACT The PSE-4 enzyme is a prototype carbenicillin-hydrolyzing enzyme exhibiting high activity against penicillins and early cephalosporins. To understand the mechanism that modulates substrate profiles and to verify the ability of PSE-4 to extend its substrate specificity toward expanded-spectrum cephalosporins, we used random replacement mutagenesis to generate six random libraries from amino acids 162 to 179 in the Ω loop. This region is known from studies with TEM-1 to be implicated in substrate specificity. It was found that the mechanism modulating ceftazidime hydrolysis in PSE-4 was different from that in TEM-1. The specificity of class 2c carbenicillin-hydrolyzing enzymes could not be assigned to the Ω loop of PSE-4. Analysis of the percentage of functional enzymes revealed that the hydrolysis of ampicillin was more affected than hydrolysis of carbenicillin by amino acid substitutions at positions 162 to 164 and 165 to 167.

scholarly journals Gain-of-function mutations identify amino acids within transmembrane domains of the yeast vacuolar transporter Zrc1 that determine metal specificity

2009 ◽  
Vol 422 (2) ◽  
pp. 273-283 ◽  
Author(s):  
Huilan Lin ◽  
Damali Burton ◽  
Liangtao Li ◽  
David E. Warner ◽  
John D. Phillips ◽  
...  
Keyword(s):  
Amino Acid ◽  
Substrate Specificity ◽  
Binding Site ◽  
Iron Toxicity ◽  
Transmembrane Domains ◽  
Single Amino Acid ◽  
Amino Acid Substitutions ◽  
Transport Activity ◽  
Metal Specificity ◽  
High Iron

Cation diffusion facilitator transporters are found in all three Kingdoms of life and are involved in transporting transition metals out of the cytosol. The metals they transport include Zn2+, Co2+, Fe2+, Cd2+, Ni2+ and Mn2+; however, no single transporter transports all metals. Previously we showed that a single amino acid mutation in the yeast vacuolar zinc transporter Zrc1 changed its substrate specificity from Zn2+ to Fe2+ and Mn2+ [Lin, Kumanovics, Nelson, Warner, Ward and Kaplan (2008) J. Biol. Chem. 283, 33865–33873]. Mutant Zrc1 that gained iron transport activity could protect cells with a deletion in the vacuolar iron transporter (CCC1) from high iron toxicity. Utilizing suppression of high iron toxicity and PCR mutagenesis of ZRC1, we identified other amino acid substitutions within ZRC1 that changed its metal specificity. All Zrc1 mutants that transported Fe2+ could also transport Mn2+. Some Zrc1 mutants lost the ability to transport Zn2+, but others retained the ability to transport Zn2+. All of the amino acid substitutions that resulted in a gain in Fe2+ transport activity were found in transmembrane domains. In addition to alteration of residues adjacent to the putative metal- binding site in two transmembrane domains, alteration of residues distant from the binding site affected substrate specificity. These results suggest that substrate selection involves co-operativity between transmembrane domains.

A New Variant with Two Amino Acid Substitutions: Hb S‐Cameroon [β6(A3)Glu→Val;β90(F6)Glu→Lys]

Hemoglobin ◽  
2004 ◽  
Vol 28 (2) ◽  
pp. 131-135 ◽  
Author(s):  
Jens R. Bundgaard ◽  
Ole W. Bjerrum ◽  
Anne Tybjærg‐Hansen
Keyword(s):  
Amino Acid ◽  
Amino Acid Substitutions ◽  
New Variant ◽  
Hb S

scholarly journals Emergence in Southern France of a new SARS-CoV-2 variant of probably Cameroonian origin harbouring both substitutions N501Y and E484K in the spike protein

2021 ◽  
Author(s):  
Philippe Colson ◽  
Jeremy Delerce ◽  
Emilie Burel ◽  
Jordan Dahan ◽  
Agnes Jouffret ◽  
...  
Keyword(s):  
Amino Acid ◽  
Geographical Area ◽  
Sister Group ◽  
Spike Protein ◽  
Phylogenetic Position ◽  
Amino Acid Substitutions ◽  
Nucleotide Substitutions ◽  
Oxford Nanopore ◽  
New Variant ◽  
Previous Definition

SARS-CoV-2 variants have become a major virological, epidemiological and clinical concern, particularly with regard to the risk of escape from vaccine-induced immunity. Here we describe the emergence of a new variant. For twelve SARS-CoV-positive patients living in the same geographical area of southeastern France, qPCR testing that screen for variant-associated mutations showed an atypical combination. The index case returned from a travel in Cameroon. The genomes were obtained by next-generation sequencing with Oxford Nanopore Technologies on GridION instruments within approximately 8 h. Their analysis revealed 46 mutations and 37 deletions resulting in 30 amino acid substitutions and 12 deletions. Fourteen amino acid substitutions, including N501Y and E484K, and 9 deletions are located in the spike protein. This genotype pattern led to create a new Pangolin lineage named B.1.640.2, which is a phylogenetic sister group to the old B.1.640 lineage renamed B.1.640.1. Both lineages differ by 25 nucleotide substitutions and 33 deletions. The mutation set and phylogenetic position of the genomes obtained here indicate based on our previous definition a new variant we named 'IHU'. These data are another example of the unpredictability of the emergence of SARS-CoV-2 variants, and of their introduction in a given geographical area from abroad.

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