scholarly journals Quantum-Chemical Study of the Propensity of the Amino Acid Pairs for the Peptide Bond Formation

2017 ◽  
Vol 10 (1) ◽  
Author(s):  
Kereselidze J ◽  
Mikuchadze G ◽  
Bobokhidze L
Keyword(s):  
Amino Acid ◽  
Quantum Chemical ◽  
Bond Formation ◽  
Quantum Chemical Study ◽  
Chemical Study ◽  
Peptide Bond ◽  
Peptide Bond Formation

Oxidative Peptide Bond Formation of Glycine-Amino Acid using 2-(Aminomethyl)malononitrile as a Glycine Unit

2021 ◽  
Author(s):  
Xiaoling Wang ◽  
Jing Li ◽  
Yujiro Hayashi
Keyword(s):  
Aqueous Solution ◽  
Amino Acid ◽  
Bond Formation ◽  
Peptide Bond ◽  
Peptide Bond Formation ◽  
Amide Linkage

Amide linkage of glycine-amino acid was synthesized by coupling of substituted 2-(aminomethyl)malononitrile as a C-terminal glycine unit and N-terminal amine using CsOAc and O2 in aqueous solution. This is a...

Quantum chemical studies of a model for peptide bond formation: formation of formamide and water from ammonia and formic acid

1982 ◽  
Vol 104 (23) ◽  
pp. 6169-6174 ◽  
Author(s):  
Tetsuro Oie ◽  
Gilda H. Loew ◽  
Stanley K. Burt ◽  
J. Stephen Binkley ◽  
Robert D. MacElroy
Keyword(s):  
Formic Acid ◽  
Quantum Chemical ◽  
Bond Formation ◽  
Peptide Bond ◽  
Peptide Bond Formation ◽  
Chemical Studies ◽  
Quantum Chemical Studies

scholarly journals Prebiotic Peptide Bond Formation Through Amino Acid Phosphorylation. Insights from Quantum Chemical Simulations

Life ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 75 ◽  
Author(s):  
Berta Martínez-Bachs ◽  
Albert Rimola
Keyword(s):  
Free Energy ◽  
Quantum Chemical ◽  
Density Functional ◽  
Bond Formation ◽  
Building Blocks ◽  
Peptide Bond ◽  
High Energy ◽  
Free Energy Barrier ◽  
Peptide Bond Formation ◽  
Condensation Reactions

Condensation reactions between biomolecular building blocks are the main synthetic channels to build biopolymers. However, under highly diluted prebiotic conditions, condensations are thermodynamically hampered since they release water. Moreover, these reactions are also kinetically hindered as, in the absence of any catalyst, they present high activation energies. In living organisms, in the formation of peptides by condensation of amino acids, this issue is overcome by the participation of adenosine triphosphate (ATP), in which, previous to the condensation, phosphorylation of one of the reactants is carried out to convert it as an activated intermediate. In this work, we present for the first time results based on density functional theory (DFT) calculations on the peptide bond formation between two glycine (Gly) molecules adopting this phosphorylation-based mechanism considering a prebiotic context. Here, ATP has been modeled by a triphosphate (TP) component, and different scenarios have been considered: (i) gas-phase conditions, (ii) in the presence of a Mg2+ ion available within the layer of clays, and (iii) in the presence of a Mg2+ ion in watery environments. For all of them, the free energy profiles have been fully characterized. Energetics derived from the quantum chemical calculations indicate that none of the processes seem to be feasible in the prebiotic context. In scenarios (i) and (ii), the reactions are inhibited due to unfavorable thermodynamics associated with the formation of high energy intermediates, while in scenario (iii), the reaction is inhibited due to the high free energy barrier associated with the condensation reactions. As a final consideration, the role of clays in this TP-mediated peptide bond formation route is advocated, since the interaction of the phosphorylated intermediate with the internal clay surfaces could well favor the reaction free energies.

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.

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