Structural characterization of free-state and product-state<i>Mycobacterium tuberculosis</i>methionyl-tRNA synthetase reveals an induced-fit ligand-recognition mechanism

Wang, Wei; Qin, Bo; Wojdyla, Justyna Aleksandra; Wang, Meitian; Gao, Xiaopan; Cui, Sheng

doi:10.1107/s2052252518008217

Cited by 11 publications

(7 citation statements)

References 54 publications

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“…Similar inconclusive claims about the validity of IF have been made for the Mycobacterium tuberculosis methionyl-tRNA synthetase from comparison of large structural changes between free and bound forms of the enzyme. 75 Multiple structures of a macromolecule in the free or bound forms are necessary to rigorously assign a binding mechanism in terms of IF or CS, as shown in the case of Na + binding to thrombin [ Fig. 5(B) ].…”

Section: If As a Mathematical Special Case Of Csmentioning

confidence: 99%

Mechanisms of ligand binding

2020

Biophysics Reviews

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Many processes in chemistry and biology involve interactions of a ligand with its molecular target. Interest in the mechanism governing such interactions has dominated theoretical and experimental analysis for over a century. The interpretation of molecular recognition has evolved from a simple rigid body association of the ligand with its target to appreciation of the key role played by conformational transitions. Two conceptually distinct descriptions have had a profound impact on our understanding of mechanisms of ligand binding. The first description, referred to as induced fit, assumes that conformational changes follow the initial binding step to optimize the complex between the ligand and its target. The second description, referred to as conformational selection, assumes that the free target exists in multiple conformations in equilibrium and that the ligand selects the optimal one for binding. Both descriptions can be merged into more complex reaction schemes that better describe the functional repertoire of macromolecular systems. This review deals with basic mechanisms of ligand binding, with special emphasis on induced fit, conformational selection, and their mathematical foundations to provide rigorous context for the analysis and interpretation of experimental data. We show that conformational selection is a surprisingly versatile mechanism that includes induced fit as a mathematical special case and even captures kinetic properties of more complex reaction schemes. These features make conformational selection a dominant mechanism of molecular recognition in biology, consistent with the rich conformational landscape accessible to biological macromolecules being unraveled by structural biology.

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Section: If As a Mathematical Special Case Of Csmentioning

confidence: 99%

Mechanisms of ligand binding

2020

Biophysics Reviews

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“… 16 MARS can also be used to detect intracellular oxidative stress and controls protein synthesis under oxidative stress. 17 However, the role of MARS during BC progression remains elusive. The aims of the present study were to compare the expression level of MARS in human BC tissues and adjacent non-cancerous tissues by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry, and to explore the association between the MARS expression level and the clinicopathological characteristics of patients with BC.…”

Section: Introductionmentioning

confidence: 99%

High methionyl–tRNA synthetase expression predicts poor prognosis in patients with breast cancer

et al. 2020

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AimsMethionyl–tRNA synthetase (MARS) is known to play a critical role in initiating translation and protection against cellular damages in vivo. The aim of this study was to clarify the role of MARS in breast cancer (BC) progression.MethodsThe expressions of MARS messenger RNA (mRNA) and protein in human BC tissues and adjacent non-cancerous tissues were detected by quantitative real-time PCR, western blot and immunohistochemistry. The prognostic potential of MARS in patients with BC was assessed by univariate and multivariate survival analyses. The association between the MARS expression and BC progression was further evaluated by the bioinformatics database of UALCAN, Gene Expression Profiling Interactive Analysis (GEPIA) and Gene Expression Database of Normal and Tumor Tissues (GENT). The role of MARS in the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of human breast cancer cell line (MCF-7 cells) was investigated after siRNA transfection.ResultsThe expression level of MARS mRNA in the fresh BC tissues was significantly higher than that in the adjacent tissues. Immunohistochemistry showed that the expression level of MARS was closely associated with the clinicopathologial parameters of patients with BC, including the HER-2 status, Ki-67 status, molecular classification, tumour grade, N stage and tumour, node, metastasis (TNM) stage, and this finding was further confirmed by UALCAN database. The Kaplan-Meier analysis showed that high MARS expression and TNM stage were predictors of poor prognosis of patients with BC. The proliferation, migration and EMT capabilities of MCF-7 cells were significantly suppressed after MARS knockdown. An overview of UALCAN, GEPIA and GENT results suggested that MARS may be an oncogene of BC, as well as a potential therapeutic target of this malignant tumour.ConclusionsHigh expression level of MARS in the human BC tissues was significantly associated with the unfavourable prognosis of patients with BC, suggesting that MARS may serve as a potential prognostic marker for the clinical diagnosis and prognostic prediction of BC.

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“…In the ligand-free state, the methionine pocket adopts an enlarged configuration (Figs. 3D and 4A) also noticed in type 1 and type 2 MetRS from other organisms (48,58,59). Upon methionine binding, however, the pocket undergoes marked conformational changes involving rotamer adjustments of residues W253 and Y13 to enclose the substrate (Figs.…”

Section: Crystal Structures Of Xcmetrs In Its Ligand-free State and Bound To L-metmentioning

confidence: 75%

Molecular basis for diaryldiamine selectivity and competition with tRNA in a type 2 methionyl-tRNA synthetase from a Gram-negative bacterium

Mercaldi

Andrade

Zanella

et al. 2021

Journal of Biological Chemistry

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Structural characterization of free-state and product-stateMycobacterium tuberculosismethionyl-tRNA synthetase reveals an induced-fit ligand-recognition mechanism

Abstract: Structural characterization of M. tuberculosis methionyl-tRNA synthetase provides valuable information for antibacterial drug development.

Cited by 11 publications

References 54 publications

Mechanisms of ligand binding

Mechanisms of ligand binding

High methionyl–tRNA synthetase expression predicts poor prognosis in patients with breast cancer

Molecular basis for diaryldiamine selectivity and competition with tRNA in a type 2 methionyl-tRNA synthetase from a Gram-negative bacterium

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