Functional role of putative critical residues in Mycobacterium tuberculosis RNase P protein

2016 ◽  
Vol 78 ◽  
pp. 141-148 ◽  
Author(s):  
Alla Singh ◽  
Shah Ubaid-ullah ◽  
Janendra K. Batra
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Functional Role ◽  
Rnase P ◽  
P Protein ◽  
Critical Residues

scholarly journals Co-infections as Modulators of Disease Outcome: Minor Players or Major Players?

2021 ◽  
Vol 12 ◽  
Author(s):  
Priti Devi ◽  
Azka Khan ◽  
Partha Chattopadhyay ◽  
Priyanka Mehta ◽  
Shweta Sahni ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mycobacterium Tuberculosis ◽  
Immune System ◽  
Disease Severity ◽  
Functional Role ◽  
Biological Models ◽  
Immunological Responses ◽  
Immunodeficiency Virus ◽  
Physiological Outcome

Human host and pathogen interaction is dynamic in nature and often modulated by co-pathogens with a functional role in delineating the physiological outcome of infection. Co-infection may present either as a pre-existing pathogen which is accentuated by the introduction of a new pathogen or may appear in the form of new infection acquired secondarily due to a compromised immune system. Using diverse examples of co-infecting pathogens such as Human Immunodeficiency Virus, Mycobacterium tuberculosis and Hepatitis C Virus, we have highlighted the role of co-infections in modulating disease severity and clinical outcome. This interaction happens at multiple hierarchies, which are inclusive of stress and immunological responses and together modulate the disease severity. Already published literature provides much evidence in favor of the occurrence of co-infections during SARS-CoV-2 infection, which eventually impacts the Coronavirus disease-19 outcome. The availability of biological models like 3D organoids, mice, cell lines and mathematical models provide us with an opportunity to understand the role and mechanism of specific co-infections. Exploration of multi-omics-based interactions across co-infecting pathogens may provide deeper insights into their role in disease modulation.

scholarly journals Protein activation of a ribozyme: the role of bacterial RNase P protein

2005 ◽  
Vol 24 (19) ◽  
pp. 3360-3368 ◽  
Author(s):  
Amy H Buck ◽  
Andrew B Dalby ◽  
Alexander W Poole ◽  
Alexei V Kazantsev ◽  
Norman R Pace
Keyword(s):  
Rnase P ◽  
Protein Activation ◽  
P Protein

scholarly journals Functional Role of Methylation of G518 of the 16S rRNA 530 Loop by GidB in Mycobacterium tuberculosis

2013 ◽  
Vol 57 (12) ◽  
pp. 6311-6318 ◽  
Author(s):  
Sharon Y. Wong ◽  
Babak Javid ◽  
Balasubrahmanyam Addepalli ◽  
Grzegorz Piszczek ◽  
Michael Brad Strader ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
16S Rrna ◽  
Functional Role ◽  
High Performance ◽  
Protein Translation ◽  
Titration Calorimetry ◽  
Wild Type ◽  
Content Type ◽  
Wobble Position

ABSTRACTPosttranscriptional modifications of bacterial rRNA serve a variety of purposes, from stabilizing ribosome structure to preserving its functional integrity. Here, we investigated the functional role of one rRNA modification in particular—the methylation of guanosine at position 518 (G518) of the 16S rRNA inMycobacterium tuberculosis. Based on previously reported evidence that G518 is located 5 Å; from proline 44 of ribosomal protein S12, which interacts directly with the mRNA wobble position of the codon:anticodon helix at the A site during translation, we speculated that methylation of G518 affects protein translation. We transformed reporter constructs designed to probe the effect of functional lesions at one of the three codon positions on translational fidelity into the wild-type strain, H37Rv, and into a ΔgidBmutant, which lacks the methyltransferase (GidB) that methylates G518. We show that mistranslation occurs less in the ΔgidBmutant only in the construct bearing a lesion in the wobble position compared to H37Rv. Thus, the methylation of G518 allows mistranslation to occur at some level in order for translation to proceed smoothly and efficiently. We also explored the role of methylation at G518 in altering the susceptibility ofM. tuberculosisto streptomycin (SM). Using high-performance liquid chromatography–tandem mass spectrometry (HPLC-MS/MS), we confirmed that G518 is not methylated in the ΔgidBmutant. Furthermore, isothermal titration calorimetry experiments performed on 70S ribosomes purified from wild-type and ΔgidBmutant strains showed that methylation significantly enhances SM binding. These results provide a mechanistic explanation for the low-level, SM-resistant phenotype observed inM. tuberculosisstrains that contain agidBmutation.

scholarly journals Kinetic mechanism of human mitochondrial RNase P

2019 ◽  
Author(s):  
Xin Liu ◽  
Nancy Wu ◽  
Aranganathan Shanmuganathan ◽  
Bradley P. Klemm ◽  
Michael J. Howard ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Rnase P ◽  
Kinetic Mechanism ◽  
Ribonuclease P ◽  
Substrate Affinity ◽  
P Protein ◽  
Binding Data ◽  
Catalytically Active

ABSTRACTA first step in processing mitochondrial precursor tRNA (pre-tRNA) is cleavage of the 5’ leader catalyzed by ribonuclease P (RNase P). Human mitochondrial RNase P (mtRNase P) is composed of three protein subunits: mitochondrial RNase P protein (MRPP) 1, 2 and 3. Even though MRPP3 is the metallonuclease subunit responsible for catalysis, cleavage is observed only in the presence of the MRPP1/2 subcomplex. To understand the functional role of MRPP1/2, we reconstituted human mitochondrial RNase P in vitro and performed kinetic and thermodynamic analyses. MRPP1/2 significantly enhances both the catalytic activity and the apparent substrate affinity of mtRNase P. Additionally, pull-down and binding data demonstrate synergy between binding pre-tRNA and formation of a catalytically active MRPP1/2/3 complex. These data suggest that conformational changes in the MRPP1/2-pre-tRNA complex lead to protein-protein or protein-RNA interactions that increase both MRPP3 recognition and cleavage efficiency. This work presents the first kinetic model for human mtRNase P, providing a fundamental framework for the function of MRPP1/2 for recognition and processing of pre-tRNA.

scholarly journals A functional role of Rv1738 in Mycobacterium tuberculosis persistence suggested by racemic protein crystallography

2015 ◽  
Vol 112 (14) ◽  
pp. 4310-4315 ◽  
Author(s):  
Richard D. Bunker ◽  
Kalyaneswar Mandal ◽  
Ghader Bashiri ◽  
Jessica J. Chaston ◽  
Bradley L. Pentelute ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Mycobacterium Tuberculosis ◽  
Functional Role ◽  
3D Structure ◽  
Latent Tuberculosis ◽  
Racemic Mixture ◽  
Powerful Predictor ◽  
Ab Initio Approach ◽  
Ribosomal Protein Synthesis

Protein 3D structure can be a powerful predictor of function, but it often faces a critical roadblock at the crystallization step. Rv1738, a protein from Mycobacterium tuberculosis that is strongly implicated in the onset of nonreplicating persistence, and thereby latent tuberculosis, resisted extensive attempts at crystallization. Chemical synthesis of the l- and d-enantiomeric forms of Rv1738 enabled facile crystallization of the d/l-racemic mixture. The structure was solved by an ab initio approach that took advantage of the quantized phases characteristic of diffraction by centrosymmetric crystals. The structure, containing l- and d-dimers in a centrosymmetric space group, revealed unexpected homology with bacterial hibernation-promoting factors that bind to ribosomes and suppress translation. This suggests that the functional role of Rv1738 is to contribute to the shutdown of ribosomal protein synthesis during the onset of nonreplicating persistence of M. tuberculosis.

scholarly journals Dissecting the Role of Critical Residues and Substrate Preference of a Fatty Acyl-CoA Synthetase (FadD13) of Mycobacterium tuberculosis

PLoS ONE ◽  
2009 ◽  
Vol 4 (12) ◽  
pp. e8387 ◽  
Author(s):  
Garima Khare ◽  
Vibha Gupta ◽  
Rakesh K. Gupta ◽  
Radhika Gupta ◽  
Rajiv Bhat ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Fatty Acyl ◽  
Substrate Preference ◽  
Critical Residues
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