peptide-bond-is-amide-bond Peptide bond isomerization refers to the crucial process where the peptide bond within a protein or peptide chain changes its configuration, most commonly between *cis* and *trans* forms. This seemingly small molecular rearrangement plays a fundamental role in protein structure, influencing protein folding, refolding, and ultimately, biological activity. While all peptide bonds can isomerize, those involving proline residues are particularly significant due to their slower isomerization rates, often acting as kinetic bottlenecks in protein folding pathways. Understanding the dynamics and factors affecting peptide bond isomerization is essential for comprehending protein behavior and developing strategies for protein engineering and drug design.
A peptide bond, formed between two amino acids, possesses a partial double bond character due to resonance.作者：JR Alger·1977·被引用次数：96—Investigation ofPeptide Bond Isomerizationby Magnetization. Transfer NMR. Magnetization transfer NMR techniques have proved useful for estimating the rates. This characteristic restricts rotation around the C-N bond, leading to two possible geometric isomers: *cis* and *trans*.Chemical aspects of peptide bond isomerisation In the *trans* configuration, the alpha-carbon atoms of the adjacent amino acids are on opposite sides of the peptide bond, which is the more energetically stable and predominant form in most proteins作者：C Neale·2016·被引用次数：22—Here, we show that three classical atomistic force fields (AMBER99SB-ILDN, CHARMM22/CMAP, and OPLS-AA/L) permitpeptide bond isomerizationevery 10-50 .... The *cis* configuration places the alpha-carbon atoms on the same side, a less favored but still significant state.Characterization of Secondary Amide Peptide Bonds ... - PMC
The transition between these two configurations, known as peptide bond isomerization, is a fundamental property of natural peptides and proteins. While the *trans* isomer is favored, the *cis* isomer can exist, particularly at specific proline residues. The equilibrium between these isomers and the kinetics of their interconversion are critical. For non-proline peptide bonds, isomerization is generally rapid, occurring on the nanosecond timescale. However, when proline is involved, the isomerization rate significantly slows down, often extending to milliseconds or even longer. This slower rate for prolyl peptide bonds is a key factor in understanding the folding kinetics of many proteins.The cation-induced prolylpeptide bond isomerizationat E190-P191 (P186 in MBP-A) allows these C-type lectins to preferentially adopt the active cis-form, ...
Proline's cyclic side chain structure imposes unique constraints on the peptide bond it forms. The nitrogen atom of the peptide bond preceding proline is part of a five-membered ring, which sterically hinders the *cis* conformation. Despite this, the *cis* isomer of a prolyl peptide bond can exist, and its formation is often the rate-limiting step in the refolding of denatured proteins. This phenomenon means that even if a protein achieves its correct overall sequence of amino acids, its final functional three-dimensional structure may be delayed by the slow isomerization of one or more proline peptide bonds.
The importance of proline isomerization is further highlighted by the existence of specific enzymes called prolyl isomerases (or peptidyl-prolyl isomerases, PPIases). These enzymes catalyze the cis-trans isomerization of proline peptide bonds, significantly accelerating the process and allowing proteins to reach their native conformations more rapidlyCharacterization of secondary amide peptide bond .... PPIases are targets for various drugs, including immunosuppressants like cyclosporin and FK506, which bind to cyclophilins and FK506-binding proteins, respectively, both classes of PPIases.In the unfolded state of proteins, thepeptide groups are free to isomerizeand adopt both isomers; however, in the folded state, only a single isomer is ... This underscores the critical role of prolyl isomerization in biological systems.作者：E Masoumzadeh·2024·被引用次数：6—Proline isomerizationis widely recognized as a kinetic bottleneck in protein folding, amplified for proteins rich in Pro residues.
Several factors can influence the rate and equilibrium of peptide bond isomerization.The cation-induced prolylpeptide bond isomerizationat E190-P191 (P186 in MBP-A) allows these C-type lectins to preferentially adopt the active cis-form, ... Temperature is a significant factor; higher temperatures, as observed in high-temperature simulations, can accelerate isomerization rates, allowing for more frequent transitions between *cis* and *trans* forms. Similarly, the surrounding chemical environment, including pH and the presence of specific ions or molecules, can affect the energetics of the peptide bond and influence its isomerization.
Computational studies, such as those employing atomistic force fields, have been instrumental in quantifying the rates of peptide bond isomerization, even at elevated temperaturesRegulation of peptide bond cis/trans isomerization by .... These simulations can reveal how different force fields model these dynamics and provide insights into the timescales of isomerization for various peptide sequences, including those with and without proline residues. Understanding these computational models is crucial for interpreting simulation data accuratelyPeptide bond.
Furthermore, the local sequence context surrounding a proline residue can play a role. For instance, the specific amino acid preceding proline can influence the stability of the *cis* or *trans* isomer. Research has also explored the impact of modifications, such as alpha-methylation of proline, which can constrain the prolyl peptide bond, often favoring the *trans* conformation and potentially altering folding pathways.作者：JR Alger·1977·被引用次数：96—Investigation ofPeptide Bond Isomerizationby Magnetization. Transfer NMR. Magnetization transfer NMR techniques have proved useful for estimating the rates.
While proline-containing peptide bonds are famously slow to isomerize, non-prolyl peptide bonds can also undergo cis-trans isomerization, albeit typically at much faster rates. In some cases, the isomerization of non-proline peptide bonds can also control biological activity, indicating that this phenomenon is not solely confined to proline residues. The specific structural context and the nature of the adjacent amino acids can influence the isomerization kinetics of non-prolyl peptide bonds.
The implications of peptide bond isomerization extend to various biological processesStudy of the cis-trans Isomerization of the Amino-Acyl prolyl .... In protein folding, as mentioned, it can dictate the speed at which a protein achieves its native state.Chemical aspects of peptide bond isomerisation In protein function, the *cis* or *trans* conformation of a peptide bond can be critical for enzyme activity, receptor binding, or protein-protein interactions. For example, a specific *cis* or *trans* configuration might be required for a protein to adopt an active conformation or to bind to a particular substrate or ligand.Cis/trans isomerization of proline peptide bonds in the ...
Moreover, peptide bond isomerization is relevant in understanding protein degradation and stability.Cis/trans configurations of the peptide C - N bonds The transition between isomers can sometimes be linked to peptide bond cleavage, particularly at specific residues like aspartic acid, under certain conditions. The study of peptide ion isomerization and fragmentation is also fundamental for techniques like peptide sequencing, where understanding how peptides rearrange and break apart provides crucial information about their amino acid sequence.
Peptide bond isomerization, encompassing the interconversion between *cis* and *trans* configurations, is a fundamental molecular process with profound implications for protein structure, folding, and function. While generally rapid for most peptide bonds, the slower isomerization rates associated with proline residues often act as critical kinetic checkpoints in protein foldingRole of proline peptide bond isomerization in unfolding .... The existence and activity of prolyl isomerases highlight the biological significance of this process作者：C Neale·2016·被引用次数：22—We quantify therates of peptide bond isomerizationin high-temperature simulations of three octameric peptides and a small fast-folding protein.. Factors such as temperature, sequence context, and chemical environment all influence isomerization dynamicsTo search for an inductive effect on the rate of cis–trans prolylpeptide bond isomerization(eq 1), we measured these rates for 1 and 3 in dioxane47 and 1 and .... Continued research into peptide bond isomerization, through experimental techniques and computational simulations, is vital for advancing our understanding of protein science and developing novel therapeutic and biotechnological applications作者：FX Schmid·1986·被引用次数：106—ABSTRACT. Theisomerization of the proline peptide bondbetween tyrosine-92 and proline-93 in bovine pancreatic ribonu- clease A has been investigated in ....
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