The concept of molecular machines in biology has transformed the medical field in a profound way. Many essential processes that occur in the cell, including transcription, translation, protein folding and protein degradation, are all carried out by molecular machines. This volume focuses on important molecular machines whose architecture is known and whose functional principles have been established by tools of biophysical imaging (X-ray crystallography and cryo-electron microscopy) and fluorescence probing (single-molecule FRET). This edited volume includes contributions from prominent scientists and researchers who understand and have explored the structure and functions of these machines. This book is essential for students and professionals in the medical field who want to learn more about molecular machines.

Molecular machine

Folding (DSP implementation)

10.1017/cbo9781139003704

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Faculty Opinions recommendation of Single-molecule investigations of the stringent response machinery in living bacterial cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2011)

Ruben L. Gonzalez Daniel MacDougall Margaret Elvekrog

10.3410/f.13146956.14742124

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Faculty Opinions recommendation of Visualization of two transfer RNAs trapped in transit during elongation factor G-mediated translocation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2014)

Ruben L. Gonzalez Margaret Elvekrog Daniel MacDougall

Elongation

Transit time

10.3410/f.718203510.793495512

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Faculty Opinions recommendation of Real-time tRNA transit on single translating ribosomes at codon resolution.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2010)

Ruben L. Gonzalez Daniel MacDougall Margaret Elvekrog

Translation by the ribosome occurs by a complex mechanism involving the coordinated interaction of multiple nucleic acid and protein ligands. Here we use zero-mode waveguides (ZMWs) and sophisticated detection instrumentation to allow real-time observation of translation at physiologically relevant micromolar ligand concentrations. Translation at each codon is monitored by stable binding of transfer RNAs (tRNAs)-labelled with distinct fluorophores-to translating ribosomes, which allows direct detection of the identity of tRNA molecules bound to the ribosome and therefore the underlying messenger RNA (mRNA) sequence. We observe the transit of tRNAs on single translating ribosomes and determine the number of tRNA molecules simultaneously bound to the ribosome, at each codon of an mRNA molecule. Our results show that ribosomes are only briefly occupied by two tRNA molecules and that release of deacylated tRNA from the exit (E) site is uncoupled from binding of aminoacyl-tRNA site (A-site) tRNA and occurs rapidly after translocation. The methods outlined here have broad application to the study of mRNA sequences, and the mechanism and regulation of translation. PMID: 20393556 Funding information This work was supported by: NIGMS NIH HHS, United States Grant ID: GM51266 NIGMS NIH HHS, United States Grant ID: R01 GM051266

T arm

10.3410/f.3801958.3743054

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Faculty Opinions recommendation of Three sites and you are out: ternary synergistic allostery controls aromatic amino acid biosynthesis in Mycobacterium tuberculosis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature (2013)

Ruben L. Gonzalez Margaret Elvekrog Daniel MacDougall

3-Deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) catalyzes the first step in the shikimate pathway, the pathway responsible for the biosynthesis of the aromatic amino acids Trp, Phe, and Tyr. Unlike many other organisms that produce up to three isozymes, each feedback-regulated by one of the aromatic amino acid pathway end products, Mycobacterium tuberculosis expresses a single DAH7PS enzyme that can be controlled by combinations of aromatic amino acids. This study shows that the synergistic inhibition of this enzyme by a combination of Trp and Phe can be significantly augmented by the addition of Tyr. We used X-ray crystallography, mutagenesis, and isothermal titration calorimetry studies to show that DAH7PS from M. tuberculosis possesses a Tyr-selective site in addition to the Trp and Phe sites, revealing an unusual and highly sophisticated network of three synergistic allosteric sites on one enzyme. This ternary inhibitory response, by a combination of all three aromatic amino acids, allows a tunable response of the protein to changing metabolic demands.Copyright © 2013 Elsevier Ltd. All rights reserved. PMID: 23274137

Shikimate pathway

Isothermal Titration Calorimetry

10.3410/f.718131084.793484816

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