Oligonucleotide promoted peptide bond formation using a tRNA mimicking approach

2017 ◽  
Vol 53 (36) ◽  
pp. 5013-5016
Author(s):  
H.-P. Mattelaer ◽  
C.-A. Mattelaer ◽  
N. Papastavrou ◽  
W. Dehaen ◽  
P. Herdewijn
Keyword(s):  
Nucleic Acids ◽  
Bond Formation ◽  
Protein Translation ◽  
Peptide Bond ◽  
Simplified Model ◽  
Peptide Bond Formation ◽  
Hybrid Species ◽  
Leaving Group

TransferRNA's role in protein translation is the prime example of an Informational Leaving Group (ILG). A simplified model produced oligophenylalanine with a modified uracil as an ILG in the presence of specific oligonucleotides. Our preliminary studies contribute to the importance of hybrid species in bridging the gap between peptides and nucleic acids.

Biochemistry instructors’ use of intentions for student learning to evaluate and select external representations of protein translation

2019 ◽  
Vol 20 (4) ◽  
pp. 787-803
Author(s):  
Thomas J. Bussey ◽  
MaryKay Orgill
Keyword(s):  
Student Learning ◽  
Visual Cues ◽  
Bond Formation ◽  
Protein Translation ◽  
Peptide Bond ◽  
External Representation ◽  
External Representations ◽  
Peptide Bond Formation ◽  
Scientific Phenomena ◽  
Selection Of

Instructors draw on their intentions for student learning in the enactment of curriculum, particularly in the selection and presentation of external representation of scientific phenomena. These representations both create opportunities for students to experience non-experiential biochemical phenomena, such as protein translation, and constrain the possibilities for student learning based on the limited number of features depicted and the visual cues used to draw viewers attention to those features. In this study, we explore biochemistry instructors’ intentions for student learning about protein translation and how those intentions influence their selection of external representations for instruction. A series of instructor interviews were used to identify information that students need to know in order to develop a biochemically accurate understanding of protein translation. We refer to this information as the “critical features” of protein translation. Two dominant themes of critical features were identified: (1) components/structures of protein translation and (2) interactions/chemistry of protein translation. Three general components (the ribosome, the mRNA, and the tRNA) and two primary interactions (base pairing and peptide bond formation) were described by all instructors. Instructors tended to favor simpler, stylized representations that closely aligned with their stated critical features of translation for instructional purposes.

scholarly journals Abstract P-29: Cryoem Study of the Inhibition of Bacterial Ribosomes by Madumycin II

2021 ◽  
Vol 11 (Suppl_1) ◽  
pp. S24-S25
Author(s):  
Alena Yakusheva ◽  
Olga Shulenina ◽  
Evgeny Pichkur ◽  
Alena Paleskava ◽  
Alexander Myasnikov ◽  
...  
Keyword(s):  
Amino Acid ◽  
High Resolution ◽  
Bond Formation ◽  
Protein Translation ◽  
Peptide Bond ◽  
Peptide Bond Formation ◽  
Peptidyl Transferase ◽  
Peptidyl Transferase Center ◽  
70S Ribosome ◽  
Madumycin Ii

Background: The efficiency of widely used antibiotics is limited by continuous improvement of resistance mechanisms. Thus, the research of poorly studied drugs that have not received practical use until now becomes relevant again. Protein translation is one of the major targets for antibiotics. Madumycin II (MADU) is an antibiotic of the streptogramin A class that binds to the peptidyl transferase center of the initiated bacterial 70S ribosome inhibiting the first cycle of peptide bond formation (I.A. Osterman et al. Nucleic Acids Res., 2017). The ability of MADU to interfere with translating ribosome is an open question that we address by investigation of high-resolution cryo-EM structures of MADU bound 70S ribosome complexes from Escherichia coli. Methods: Purified initiated and translating ribosome complexes preincubated with MADU were applied onto freshly glow discharged carbon-coated grids (Quantifoil R 1.2/1.3) and flash-frozen in the liquid ethane pre-cooled by liquid nitrogen in the Vitrobot Mark IV. Frozen grids were transferred into an in-house Titan Krios microscope. Data were collected using EPU software. Movie stacks were preprocessed in Warp software. For image processing, we have used several software packages: Relion 3.1, CryoSPARC, and CisTEM. The model was built in Coot. Results: We have obtained high-resolution cryo-EM structures of two ribosomal complexes with MADU before and after the first cycle of peptide bond formation with an average resolution of 2.3 Å. Preliminary analysis of the structures shows no major differences in the MADU binding mode to the ribosomal complexes under study suggesting that the quantity of amino acid residues attached to the P-site tRNA does not impact MADU bonding. Moreover, in both cases, we observed similar destabilization of the CCA-ends of A- and P-site tRNAs underlining the comparable influence of MADU on the ribosomal complexes. Conclusion: Our results suggest that although MADU binding site is located in the peptidyl transferase center, the presence of the second amino acid residue on the P-site tRNA does not preclude antibiotic binding. We assume that further elongation of the polypeptide chain would not have any impact either. High conformational lability of the CCA-ends of tRNA at the A and P sites upon binding of MADU obviously plays an important role in the inhibition mechanism of the bacterial ribosome. The further structural and biochemical analysis will be necessary to shed more light on the detailed mechanism of MADU action.

Beyond peptide bond formation: the versatile role of condensation domains in natural product biosynthesis

2021 ◽  
Author(s):  
Sofie Dekimpe ◽  
Joleen Masschelein
Keyword(s):  
Natural Product ◽  
Bond Formation ◽  
Peptide Bond ◽  
Chemical Diversity ◽  
Peptide Bond Formation ◽  
Natural Product Biosynthesis

Condensation domains perform highly diverse functions during natural product biosynthesis and are capable of generating remarkable chemical diversity.

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