Comparison of the Intrinsic Dynamics of Aminoacyl-tRNA Synthetases

Abstract

Aminoacyl-tRNA synthetases (AARSs) are an important family of enzymes that catalyze tRNA aminoacylation reaction (Ibba and Soll in Annu Rev Biochem 2000, 69:617-650) [1]. AARSs are grouped into two broad classes (class I and II) based on sequence/structural homology and mode of their interactions with the tRNA molecule (Ibba and Soll in Annu Rev Biochem 2000, 69:617-650) [1]. As protein dynamics play an important role in enzyme function, we explored the intrinsic dynamics of these enzymes using normal mode analysis and investigated if the two classes and six subclasses (Ia-c and IIa-c) of AARSs exhibit any distinct patterns of motion. The present study found that the intrinsic dynamics-based classification of these enzymes is similar to that obtained based on sequence/structural homology for most enzymes. However, the classification of seryl-tRNA synthetase was not straightforward; the internal mobility patterns of this enzyme are comparable to both IIa and IIb AARSs. This study revealed only a few general mobility patterns in these enzymes--(1) the insertion domain is generally engaged in anticorrelated motion with respect to the catalytic domain for both classes of AARSs and (2) anticodon binding domain dynamics are partly correlated and partly anticorrelated with respect to other domains for class I enzymes. In most of the class II AARSs, the anticodon binding domain is predominately engaged in anticorrelated motion with respect to the catalytic domain and correlated to the insertion domain. This study supports the notion that dynamic-based classification could be useful for functional classification of proteins.

Comparison of intrinsic dynamics of cytochrome p450 proteins using normal mode analysis

“…and ) and they exhibit distinctly different patterns of motions compared to proteins from different classes, e.g. aminoacyl‐tRNA synthetases . It can also be noted that the CYP proteins classification is based on their redox partner, and therefore the observed dynamic differences are not entirely unexpected.…”

“…aminoacyl-tRNA synthetases. 31 It can also be noted that the CYP proteins classification is based on their redox partner, and therefore the observed dynamic differences are not entirely unexpected. Because the P450-only proteins do not rely on common interactions with auxiliary electron transport proteins to perform their catalytic function, their sequence, structural, and dynamic motifs are likely more reliant on individual substrate specificity and catalytic mechanism, whereas proteins in other CYP classes maintain conserved properties for interactions with their redox partners.…”

“…Even though coarse‐grained NMA is unable to provide a detailed description of local dynamics that are obtained from all‐atom molecular dynamic simulations, coarse‐grained NMA has been shown to be equally capable of illustrating the functional global motions of proteins that are defined by the overall architecture . NMA‐based methods have thus become widely used in the exploration of whole‐protein and domain‐specific motions of individual proteins, and they have also been used to probe the related dynamic motifs existing within protein superfamilies …”

Incorporating modeling and simulations in undergraduate biophysical chemistry course to promote understanding of structure‐dynamics‐function relationships in proteins

“…Protein dynamics and their impact on protein function have been the main focus of our research in the past several years [58,59,[61][62][63][64][65]. Several undergraduate researchers have collaborated in various projects dealing with fundamental questions on the role of protein motions in relation to their function.…”

Comparing the intrinsic dynamics of multiple protein structures using elastic network models

“…Studies like this have also prompted initiatives to categorise protein structures dynamically [105]. Further databases storing results from normal mode analysis using ENMs on large number of structures have been built, such as ProMode Elastic [46] or MolmovDB (Database of Macromolecular Movement) [106].…”