Finding a proper transition structure for the peptide bond formation process can lead one to a better understanding of the role of ribosome in catalyzing this reaction. Using computer simulations, we ...performed the potential energy surface scan on the ester bond dissociation of P-site aminoacyl-tRNA and the peptide bond formation of P-site and A-site amino acids. The full fragments of initiator tRNA
i
met
and elongator tRNA
phe
are attached to both cognate and non-cognate amino acids as the P-site substrate. The A-site amino acid for all four calculations is methionine. We used ONIOM calculations to reduce the computational cost. Our study illustrates the reduced rate of peptide bond formation for misacylated tRNA
i
met
in the absence of ribosomal bases. The misacylated elongator tRNA
phe
, however, did not show any difference in its PES compared with that for the phe-tRNA
phe
. This demonstrates the structural specification of initiator tRNA
i
met
for the amino acids side chain.
We review experiments colliding electrons (/positrons) on protons at high energies at HERA, focusing on the ZEUS experiment. We describe the ZEUS detector, including its data acquisition system, and ...look at a specific part, namely the electronic system for its calorimeter readout control, in more detail. Data analysis is described, and results pertaining the proton structure is given. It is found that the naive quark model cannot explain the results obtained at small fractional momentum, and this requires quantum chromodynamics. Also it is found that diffractive reactions, with large rapidity gaps, contribute substantially; efforts are being carried out to understand them.
Notwithstanding various unsolved questions regarding the structure and function of the ribosome, the process of peptide bond formation is of particular importance, being the heart of protein ...synthesis. Several experimental studies have been carried out on the pre- and post-peptidyl transfer structures in the ribosomal active site. Based on these structures, different reaction mechanisms have been proposed and further investigated using computational techniques. However, the detailed mechanism of peptidyl transfer, as well as the atoms and functional groups involved in this process are still in limbo. Although it was suggested that the A2451 is present in the active site of the ribosome in the previous crystallographic structures, the details of its participation have not been fully investigated. Furthermore, despite the highlighted importance of the P-site A76 2′-OH group in previous studies, its actual role during the process is still unclear. Finally, whether the process of peptidyl transfer is a stepwise mechanism or a concerted one is still under debate. Several computational mechanistic studies have been carried out to investigate the catalytic power of the ribosome, yet, they do not cover all the three concerns mentioned above. Therefore, as well as re-investigating the previously proposed reaction mechanisms with a higher level of theory and basis set (
i.e.
M06-2X/6-31++G(d,p)//M06-2X/6-311++G(d,p)) in this study, we propose three new reaction mechanisms based on three different pre- and post-peptidyl transfer structures obtained from previous experimental studies. The results of this study highlights the important role played by the P-site A76 2′-OH group in catalyzing the reaction. However, instead of acting as a so-called proton shuttle, this group acts as a polypeptidyl shuttle, transferring the growing polypeptide chain from the leaving 3′-O to the attacking nucleophile through a mechanism known as transesterification. This reaction is aided by the A2451 3′-OH rRNA base, acting as a proton shuttle between the P-site 3′-O and the 2′-O and further stabilizing the transition structure.
The P-site-A76-2′OH transfers the polypeptide chain to the A-site α-amine and A2451 facilitates this transfer by acting as proton shuttle.
Beyong the Higgs Abdullah, Wan Ahmad Tajuddin Wan
arXiv.org,
12/2012
Paper, Journal Article
Odprti dostop
A Higgs-compatible boson has been observed at the LHC at CERN. We briefly review the role of the Higgs in particle physics and describe some of the current challenges in understanding the fundamental ...structure of the universe. Is there supersymmetry and is it instrumental in uniting gravity with the other three fundamental forces? What makes up dark matter and dark energy? We also report on the efforts in experimental particle physics by Malaysian collaborators to answer some of these questions.
The proper arrangement of amino acids in a protein determines its proper function, which is vital for the cellular metabolism. This indicates that the process of peptide bond formation requires high ...fidelity. One of the most important processes for this fidelity is kinetic proofreading. As biochemical experiments suggest that kinetic proofreading plays a major role in ensuring the fidelity of protein synthesis, it is not certain whether or not a misacylated tRNA would be corrected by kinetic proofreading during the peptide bond formation. Using 2-layered ONIOM (QM/MM) computational calculations, we studied the behavior of misacylated tRNAs and compared the results with these for cognate aminoacyl-tRNAs during the process of peptide bond formation to investigate the effect of nonnative amino acids on tRNAs. The difference between the behavior of initiator tRNA
i
met
compared to the one for the elongator tRNAs indicates that only the initiator tRNA
i
met
specifies the amino acid side chain.
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