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[PMID]:29200433
[Au] Autor:Jeong HJ; Abhiraman GC; Story CM; Ingram JR; Dougan SK
[Ad] Endereço:Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
[Ti] Título:Generation of Ca2+-independent sortase A mutants with enhanced activity for protein and cell surface labeling.
[So] Source:PLoS One;12(12):e0189068, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Sortase A, a calcium-dependent transpeptidase derived from Staphylococcus aureus, is used in a broad range of applications, such as the conjugation of fluorescent dyes and other moieties to proteins or to the surface of eukaryotic cells. In vivo and cell-based applications of sortase have been somewhat limited by the large range of calcium concentrations, as well as by the often transient nature of protein-protein interactions in living systems. In order to use sortase A for cell labeling applications, we generated a new sortase A variant by combining multiple mutations to yield an enzyme that was both calcium-independent and highly active. This variant has enhanced activity for both N- and C-terminal labeling, as well as for cell surface modification under physiological conditions.
[Mh] Termos MeSH primário: Aminoaciltransferases/genética
Proteínas de Bactérias/genética
Cálcio/metabolismo
Cisteína Endopeptidases/genética
Peptidil Transferases/genética
Coloração e Rotulagem/métodos
Staphylococcus aureus/genética
[Mh] Termos MeSH secundário: Aminoaciltransferases/metabolismo
Proteínas de Bactérias/metabolismo
Membrana Celular/química
Cisteína Endopeptidases/metabolismo
Mutação
Peptidil Transferases/metabolismo
Staphylococcus aureus/enzimologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); EC 2.3.2.- (Aminoacyltransferases); EC 2.3.2.- (sortase A); EC 2.3.2.12 (Peptidyl Transferases); EC 3.4.22.- (Cysteine Endopeptidases); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171229
[Lr] Data última revisão:
171229
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189068


  2 / 2384 MEDLINE  
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[PMID]:28786485
[Au] Autor:Agmon I
[Ad] Endereço:Institute for Advanced Studies in Theoretical Chemistry, Schulich Faculty of Chemistry, Technion - Israel Institute of Technology, Haifa, Israel.
[Ti] Título:Sequence complementarity at the ribosomal Peptidyl Transferase Centre implies self-replicating origin.
[So] Source:FEBS Lett;591(20):3252-3258, 2017 Oct.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A feasible scenario for the emergence of life requires the spontaneous materialization and sustainability of a proto-ribosome that could have catalysed the formation of the first peptides. Models of proto-ribosomes were derived from the ribosomal Peptidyl Transferase Centre (PTC) region, but the poor prebiotic copying abilities give rise to the question of their mode of replication. Here, complementarity is demonstrated in bacterial ribosomes, between nucleotides that constitute the two halves of the PTC cavity. The complementarity corroborates the dimeric nature of the proto-ribosome and is likely to underlie the symmetry of the PTC region. Furthermore, it indicates a simple and efficient replication mode; the strand of each monomer could have acted as a template for the synthesis of its counterpart, forming a self-replicating ribozyme.
[Mh] Termos MeSH primário: Origem da Vida
Peptidil Transferases/química
RNA Catalítico/química
RNA Ribossômico 23S/química
Ribossomos/metabolismo
[Mh] Termos MeSH secundário: Pareamento de Bases
Biocatálise
Escherichia coli/genética
Escherichia coli/metabolismo
Evolução Molecular
Modelos Biológicos
Modelos Moleculares
Conformação de Ácido Nucleico
Peptidil Transferases/genética
Peptidil Transferases/metabolismo
RNA Catalítico/genética
RNA Catalítico/metabolismo
RNA Ribossômico 23S/genética
RNA Ribossômico 23S/metabolismo
Ribossomos/genética
Ribossomos/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Catalytic); 0 (RNA, Ribosomal, 23S); EC 2.3.2.12 (Peptidyl Transferases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12781


  3 / 2384 MEDLINE  
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[PMID]:28553948
[Au] Autor:Qiao Y; Srisuknimit V; Rubino F; Schaefer K; Ruiz N; Walker S; Kahne D
[Ad] Endereço:Department of Microbiology and Immunology, Harvard Medical School, Boston, Massachusetts, USA.
[Ti] Título:Lipid II overproduction allows direct assay of transpeptidase inhibition by ß-lactams.
[So] Source:Nat Chem Biol;13(7):793-798, 2017 Jul.
[Is] ISSN:1552-4469
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Peptidoglycan is an essential crosslinked polymer that surrounds bacteria and protects them from osmotic lysis. ß-lactam antibiotics target the final stages of peptidoglycan biosynthesis by inhibiting the transpeptidases that crosslink glycan strands to complete cell wall assembly. Characterization of transpeptidases and their inhibition by ß-lactams have been hampered by lack of access to a suitable substrate. We describe a general approach to accumulate Lipid II in bacteria and to obtain large quantities of this cell wall precursor. We demonstrate the utility of this strategy by isolating Staphylococcus aureus Lipid II and reconstituting the synthesis of crosslinked peptidoglycan by the essential penicillin-binding protein 2 (PBP2), which catalyzes both glycan polymerization and transpeptidation. We also show that we can compare the potencies of different ß-lactams by directly monitoring transpeptidase inhibition. The methods reported here will enable a better understanding of cell wall biosynthesis and facilitate studies of next-generation transpeptidase inhibitors.
[Mh] Termos MeSH primário: Proteínas de Bactérias/biossíntese
Proteínas de Bactérias/química
Lipídeos/química
Peptidil Transferases/antagonistas & inibidores
Staphylococcus aureus/química
Staphylococcus aureus/metabolismo
beta-Lactamas/farmacologia
[Mh] Termos MeSH secundário: Proteínas de Bactérias/isolamento & purificação
Parede Celular/efeitos dos fármacos
Parede Celular/metabolismo
Estrutura Molecular
Proteínas de Ligação às Penicilinas/química
Peptidil Transferases/metabolismo
beta-Lactamas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Lipids); 0 (Penicillin-Binding Proteins); 0 (beta-Lactams); EC 2.3.2.12 (Peptidyl Transferases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE
[do] DOI:10.1038/nchembio.2388


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[PMID]:28545389
[Au] Autor:Bianchet MA; Pan YH; Basta LAB; Saavedra H; Lloyd EP; Kumar P; Mattoo R; Townsend CA; Lamichhane G
[Ad] Endereço:Department of Neurology, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD, 21205, USA. bianchet@jhmi.edu.
[Ti] Título:Structural insight into the inactivation of Mycobacterium tuberculosis non-classical transpeptidase Ldt by biapenem and tebipenem.
[So] Source:BMC Biochem;18(1):8, 2017 May 25.
[Is] ISSN:1471-2091
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The carbapenem subclass of ß-lactams is among the most potent antibiotics available today. Emerging evidence shows that, unlike other subclasses of ß-lactams, carbapenems bind to and inhibit non-classical transpeptidases (L,D-transpeptidases) that generate 3 → 3 linkages in bacterial peptidoglycan. The carbapenems biapenem and tebipenem exhibit therapeutically valuable potencies against Mycobacterium tuberculosis (Mtb). RESULTS: Here, we report the X-ray crystal structures of Mtb L,D-transpeptidase-2 (Ldt ) complexed with biapenem or tebipenem. Despite significant variations in carbapenem sulfur side chains, biapenem and tebipenem ultimately form an identical adduct that docks to the outer cavity of Ldt . We propose that this common adduct is an enzyme catalyzed decomposition of the carbapenem adduct by a mechanism similar to S-conjugate elimination by ß-lyases. CONCLUSION: The results presented here demonstrate biapenem and tebipenem bind to the outer cavity of Ldt , covalently inactivate the enzyme, and subsequently degrade via an S-conjugate elimination mechanism. We discuss structure based drug design based on the findings and propose that the S-conjugate elimination can be leveraged to design novel agents to deliver and locally release antimicrobial factors to act synergistically with the carbapenem carrier.
[Mh] Termos MeSH primário: Mycobacterium tuberculosis/enzimologia
Peptidil Transferases/antagonistas & inibidores
[Mh] Termos MeSH secundário: Carbapenêmicos/metabolismo
Cristalografia por Raios X
Desenho de Drogas
Peptidil Transferases/química
Ligação Proteica
Tienamicinas/metabolismo
beta-Lactamas/química
beta-Lactamas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbapenems); 0 (Thienamycins); 0 (beta-Lactams); EC 2.3.2.12 (Peptidyl Transferases); Q2TWQ1I31U (tebipenem); YR5U3L9ZH1 (biapenem)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170527
[St] Status:MEDLINE
[do] DOI:10.1186/s12858-017-0082-4


  5 / 2384 MEDLINE  
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[PMID]:28525767
[Au] Autor:Park Y; Liau BB
[Ad] Endereço:Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
[Ti] Título:Uncovering the Cellular Target of Agelastatin A.
[So] Source:Cell Chem Biol;24(5):542-543, 2017 May 18.
[Is] ISSN:2451-9456
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:McClary et al. (2017) identify the eukaryotic ribosome as a cellular target of agelastatin A, resolving the long-standing mystery surrounding the cytotoxic natural product's mechanism of action. Structural and modeling studies further pinpointed the molecule's binding site to the ribosome peptidyl transferase center, revealing key molecular interactions that drive binding.
[Mh] Termos MeSH primário: Alcaloides/farmacologia
Oxazolidinonas/farmacologia
Ribossomos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Terapia de Alvo Molecular
Peptidil Transferases/metabolismo
Ribossomos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Alkaloids); 0 (Oxazolidinones); 0 (agelastatin A); EC 2.3.2.12 (Peptidyl Transferases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170707
[Lr] Data última revisão:
170707
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE


  6 / 2384 MEDLINE  
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[PMID]:28505372
[Au] Autor:Osterman IA; Khabibullina NF; Komarova ES; Kasatsky P; Kartsev VG; Bogdanov AA; Dontsova OA; Konevega AL; Sergiev PV; Polikanov YS
[Ad] Endereço:Lomonosov Moscow State University, Department of Chemistry and A.N. Belozersky Institute of Physico-Chemical Biology, Moscow 119992, Russia.
[Ti] Título:Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state.
[So] Source:Nucleic Acids Res;45(12):7507-7514, 2017 Jul 07.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The emergence of multi-drug resistant bacteria is limiting the effectiveness of commonly used antibiotics, which spurs a renewed interest in revisiting older and poorly studied drugs. Streptogramins A is a class of protein synthesis inhibitors that target the peptidyl transferase center (PTC) on the large subunit of the ribosome. In this work, we have revealed the mode of action of the PTC inhibitor madumycin II, an alanine-containing streptogramin A antibiotic, in the context of a functional 70S ribosome containing tRNA substrates. Madumycin II inhibits the ribosome prior to the first cycle of peptide bond formation. It allows binding of the tRNAs to the ribosomal A and P sites, but prevents correct positioning of their CCA-ends into the PTC thus making peptide bond formation impossible. We also revealed a previously unseen drug-induced rearrangement of nucleotides U2506 and U2585 of the 23S rRNA resulting in the formation of the U2506•G2583 wobble pair that was attributed to a catalytically inactive state of the PTC. The structural and biochemical data reported here expand our knowledge on the fundamental mechanisms by which peptidyl transferase inhibitors modulate the catalytic activity of the ribosome.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Proteínas de Bactérias/antagonistas & inibidores
Peptidil Transferases/antagonistas & inibidores
Inibidores da Síntese de Proteínas/farmacologia
RNA de Transferência/antagonistas & inibidores
Ribossomos/efeitos dos fármacos
Estreptograminas/farmacologia
[Mh] Termos MeSH secundário: Antibacterianos/química
Proteínas de Bactérias/química
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Sítios de Ligação
Domínio Catalítico
Escherichia coli/efeitos dos fármacos
Escherichia coli/enzimologia
Escherichia coli/genética
Modelos Moleculares
Conformação de Ácido Nucleico
Peptidil Transferases/química
Peptidil Transferases/genética
Peptidil Transferases/metabolismo
Biossíntese de Proteínas/efeitos dos fármacos
Inibidores da Síntese de Proteínas/química
RNA Ribossômico 23S/antagonistas & inibidores
RNA Ribossômico 23S/química
RNA Ribossômico 23S/metabolismo
RNA de Transferência/química
RNA de Transferência/metabolismo
Ribossomos/genética
Ribossomos/metabolismo
Estreptograminas/química
Thermus thermophilus/efeitos dos fármacos
Thermus thermophilus/enzimologia
Thermus thermophilus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (Protein Synthesis Inhibitors); 0 (RNA, Ribosomal, 23S); 0 (Streptogramins); 0 (madumycin II); 9014-25-9 (RNA, Transfer); EC 2.3.2.12 (Peptidyl Transferases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170516
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx413


  7 / 2384 MEDLINE  
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[PMID]:28392174
[Au] Autor:Schuller AP; Wu CC; Dever TE; Buskirk AR; Green R
[Ad] Endereço:Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
[Ti] Título:eIF5A Functions Globally in Translation Elongation and Termination.
[So] Source:Mol Cell;66(2):194-205.e5, 2017 Apr 20.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The eukaryotic translation factor eIF5A, originally identified as an initiation factor, was later shown to promote translation elongation of iterated proline sequences. Using a combination of ribosome profiling and in vitro biochemistry, we report a much broader role for eIF5A in elongation and uncover a critical function for eIF5A in termination. Ribosome profiling of an eIF5A-depleted strain reveals a global elongation defect, with abundant ribosomes stalling at many sequences, not limited to proline stretches. Our data also show ribosome accumulation at stop codons and in the 3' UTR, suggesting a global defect in termination in the absence of eIF5A. Using an in vitro reconstituted translation system, we find that eIF5A strongly promotes the translation of the stalling sequences identified by profiling and increases the rate of peptidyl-tRNA hydrolysis more than 17-fold. We conclude that eIF5A functions broadly in elongation and termination, rationalizing its high cellular abundance and essential nature.
[Mh] Termos MeSH primário: Elongação Traducional da Cadeia Peptídica
Terminação Traducional da Cadeia Peptídica
Fatores de Iniciação de Peptídeos/metabolismo
Proteínas de Ligação a RNA/metabolismo
Ribossomos/metabolismo
Proteínas de Saccharomyces cerevisiae/metabolismo
Saccharomyces cerevisiae/metabolismo
[Mh] Termos MeSH secundário: Regiões 3' não Traduzidas
Motivos de Aminoácidos
Códon de Terminação
Perfilação da Expressão Gênica/métodos
Hidrólise
Cinética
Fatores de Iniciação de Peptídeos/genética
Fatores de Terminação de Peptídeos/genética
Fatores de Terminação de Peptídeos/metabolismo
Peptídeos/metabolismo
Peptidil Transferases/genética
Peptidil Transferases/metabolismo
RNA Fúngico/genética
RNA Fúngico/metabolismo
Aminoacil-RNA de Transferência/genética
Aminoacil-RNA de Transferência/metabolismo
Proteínas de Ligação a RNA/genética
Ribossomos/genética
Saccharomyces cerevisiae/genética
Proteínas de Saccharomyces cerevisiae/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (3' Untranslated Regions); 0 (Codon, Terminator); 0 (Peptide Initiation Factors); 0 (Peptide Termination Factors); 0 (Peptides); 0 (RNA, Fungal); 0 (RNA, Transfer, Amino Acyl); 0 (RNA-Binding Proteins); 0 (SUP45 protein, S cerevisiae); 0 (Saccharomyces cerevisiae Proteins); 0 (eukaryotic translation initiation factor 5A); 0 (tRNA, peptidyl-); 25191-13-3 (polyproline); EC 2.3.2.12 (Peptidyl Transferases)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170411
[St] Status:MEDLINE


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[PMID]:28383125
[Au] Autor:Bukowska-Faniband E; Hederstedt L
[Ad] Endereço:Microbiology Group, Department of Biology, Lund University, Sölvegatan 35, Lund, SE- 223 62, Sweden.
[Ti] Título:Transpeptidase activity of penicillin-binding protein SpoVD in peptidoglycan synthesis conditionally depends on the disulfide reductase StoA.
[So] Source:Mol Microbiol;105(1):98-114, 2017 07.
[Is] ISSN:1365-2958
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Endospore cortex peptidoglycan synthesis is not required for bacterial growth but essential for endospore heat resistance. It therefore constitutes an amenable system for research on peptidoglycan biogenesis. The Bacillus subtilis sporulation-specific class B penicillin-binding protein (PBP) SpoVD and many homologous PBPs contain two conserved cysteine residues of unknown function in the transpeptidase domain - one as residue x in the SxN catalytic site motif and the other in a flexible loop near the catalytic site. A disulfide bond between these residues blocks the function of SpoVD in cortex synthesis. With a combination of experiments with purified proteins and B. subtilis mutant cells, it was shown that in active SpoVD the two cysteine residues most probably interact by hydrogen bonding and that this is important for peptidoglycan synthesis in vivo. It was furthermore demonstrated that the sporulation-specific thiol-disulfide oxidoreductase StoA reduces SpoVD and that requirement of StoA for cortex synthesis can be suppressed by two completely different types of structural alterations in SpoVD. It is concluded that StoA plays a critical role mainly during maturation of SpoVD in the forespore outer membrane. The findings advance our understanding of essential PBPs and redox control of extra-cytoplasmic protein disulfides in bacterial cells.
[Mh] Termos MeSH primário: Proteínas de Bactérias/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
Proteína Dissulfeto Redutase (Glutationa)/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Bacillus subtilis/metabolismo
Proteínas de Bactérias/genética
Parede Celular/metabolismo
Dissulfetos/metabolismo
Proteínas de Membrana/metabolismo
Proteínas de Membrana Transportadoras/genética
Oxirredutases/metabolismo
Proteínas de Ligação às Penicilinas/metabolismo
Peptidoglicano/biossíntese
Peptidoglicano/metabolismo
Peptidil Transferases/metabolismo
Esporos Bacterianos/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Disulfides); 0 (Membrane Proteins); 0 (Membrane Transport Proteins); 0 (Penicillin-Binding Proteins); 0 (Peptidoglycan); 0 (SpoVD protein, Bacillus subtilis); EC 1.- (Oxidoreductases); EC 1.8.4.2 (Protein Disulfide Reductase (Glutathione)); EC 2.3.2.12 (Peptidyl Transferases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170407
[St] Status:MEDLINE
[do] DOI:10.1111/mmi.13689


  9 / 2384 MEDLINE  
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[PMID]:28270507
[Au] Autor:Das S; Pawale VS; Dadireddy V; Singh AK; Ramakumar S; Roy RP
[Ad] Endereço:From the Department of Physics, Indian Institute of Science, Bangalore 560012, and.
[Ti] Título:Structure and specificity of a new class of Ca -independent housekeeping sortase from provide insights into its non-canonical substrate preference.
[So] Source:J Biol Chem;292(17):7244-7257, 2017 Apr 28.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Surface proteins in Gram-positive bacteria are incorporated into the cell wall through a peptide ligation reaction catalyzed by transpeptidase sortase. Six main classes (A-F) of sortase have been identified of which class A sortase is meant for housekeeping functions. The prototypic housekeeping sortase A (SaSrtA) from cleaves LP TG-containing proteins at the scissile T-G peptide bond and ligates protein-LP T to the terminal Gly residue of the nascent cross-bridge of peptidoglycan lipid II precursor. Sortase-mediated ligation ("sortagging") of LP TG-containing substrates and Gly-terminated nucleophiles occurs as well as in the presence of Ca and has been applied extensively for protein conjugations. Although the majority of applications emanate from SaSrtA, low catalytic efficiency, LP TG specificity restriction, and Ca requirement (particularly for applications) remain a drawback. Given that Gram-positive bacteria genomes encode a variety of sortases, natural sortase mining can be a viable complementary approach akin to engineering of wild-type SaSrtA. Here, we describe the structure and specificity of a new class E sortase (SavSrtE) annotated to perform housekeeping roles in Biochemical experiments define the attributes of an optimum peptide substrate, demonstrate Ca -independent activity, and provide insights about contrasting functional characteristics of SavSrtE and SaSrtA. Crystal structure, substrate docking, and mutagenesis experiments have identified a critical residue that dictates the preference for a non-canonical LA TG recognition motif over LP TG. These results have implications for rational tailoring of substrate tolerance in sortases. Besides, Ca -independent orthogonal specificity of SavSrtE is likely to expand the sortagging toolkit.
[Mh] Termos MeSH primário: Aminoaciltransferases/química
Proteínas de Bactérias/química
Cisteína Endopeptidases/química
Streptomyces/enzimologia
[Mh] Termos MeSH secundário: Motivos de Aminoácidos
Cálcio/química
Domínio Catalítico
Parede Celular/metabolismo
Clonagem Molecular
Cristalografia por Raios X
Genoma Bacteriano
Peptídeos/química
Peptidil Transferases/metabolismo
Proteínas Recombinantes/química
Staphylococcus aureus/enzimologia
Streptomyces/química
Relação Estrutura-Atividade
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Peptides); 0 (Recombinant Proteins); 0 (sortase E); EC 2.3.2.- (Aminoacyltransferases); EC 2.3.2.12 (Peptidyl Transferases); EC 3.4.22.- (Cysteine Endopeptidases); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.782037


  10 / 2384 MEDLINE  
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[PMID]:28221772
[Au] Autor:Kim SJ; Singh M; Sharif S; Schaefer J
[Ad] Endereço:Department of Chemistry and Biochemistry, Baylor University , 101 Bagby Avenue, Waco, Texas 76798, United States.
[Ti] Título:Desleucyl-Oritavancin with a Damaged d-Ala-d-Ala Binding Site Inhibits the Transpeptidation Step of Cell-Wall Biosynthesis in Whole Cells of Staphylococcus aureus.
[So] Source:Biochemistry;56(10):1529-1535, 2017 Mar 14.
[Is] ISSN:1520-4995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We have used solid-state nuclear magnetic resonance to characterize the exact nature of the dual mode of action of oritavancin in preventing cell-wall assembly in Staphylococcus aureus. Measurements performed on whole cells labeled selectively in vivo have established that des-N-methylleucyl-N-4-(4-fluorophenyl)benzyl-chloroeremomycin, an Edman degradation product of [ F]oritavancin, which has a damaged d-Ala-d-Ala binding aglycon, is a potent inhibitor of the transpeptidase activity of cell-wall biosynthesis. The desleucyl drug binds to partially cross-linked peptidoglycan by a cleft formed between the drug aglycon and its biphenyl hydrophobic side chain. This type of binding site is present in other oritavancin-like glycopeptides, which suggests that for these drugs a similar transpeptidase inhibition occurs.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Parede Celular/efeitos dos fármacos
Dipeptídeos/química
Glicopeptídeos/farmacologia
Peptidil Transferases/antagonistas & inibidores
Staphylococcus aureus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antibacterianos/química
Sítios de Ligação
Parede Celular/química
Parede Celular/enzimologia
Parede Celular/ultraestrutura
Dipeptídeos/metabolismo
Flúor/química
Flúor/metabolismo
Glicopeptídeos/química
Isótopos
Peptidoglicano/química
Peptidoglicano/metabolismo
Peptidil Transferases/metabolismo
Staphylococcus aureus/química
Staphylococcus aureus/enzimologia
Staphylococcus aureus/ultraestrutura
Vancomicina/análogos & derivados
Vancomicina/química
Vancomicina/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Dipeptides); 0 (Glycopeptides); 0 (Isotopes); 0 (Peptidoglycan); 0 (chloroeremomycin); 284SYP0193 (Fluorine); 2867-20-1 (alanylalanine); 6Q205EH1VU (Vancomycin); EC 2.3.2.12 (Peptidyl Transferases); PUG62FRZ2E (oritavancin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170714
[Lr] Data última revisão:
170714
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170222
[St] Status:MEDLINE
[do] DOI:10.1021/acs.biochem.6b01125



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