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Special Issue "NMR as a Tool to Investigate Biomolecular Structure, Recognition and Dynamics"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Bioorganic Chemistry".

Deadline for manuscript submissions: closed (10 July 2018)

Special Issue Editor

Guest Editor
Prof. Brian F. Volkman

Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
Website | E-Mail
Phone: 414-955-8400
Interests: protein structure; NMR spectroscopy; chemokine; GPCR; protein dynamics; fragment-based drug discovery; biased agonism

Special Issue Information

Dear Colleagues,

The emergent properties of living systems derive from the assembly and fluctuation of biomolecules—proteins, nucleic acids, lipids, carbohydrates—in an aqueous environment. For over 50 years, nuclear magnetic resonance (NMR) spectroscopy has been an indispensable tool in biology and its importance in translational research and clinical medicine is growing rapidly. Continual advances in isotopic labeling, instrument performance, and multidimensional NMR methods expand its range of accessibility to molecular systems of ever-increasing size and complexity, including intact cells and tissues. Solution and solid-state NMR are routinely used to solve 3D structures of biomolecular complexes, monitor ligand binding and other types of molecular recognition events, and measure molecular motions across a vast range of timescales. Chemical shifts, coupling constants, relaxation times and other NMR parameters can be combined with data from other biophysical methods and computational modeling to develop realistic descriptions of flexible molecular systems. Translational and clinical applications of NMR include chemical ligand screening for drug discovery, metabolomic analysis of plasma, urine, and cerebrospinal fluid, and FDA-approved diagnostic testing of blood lipoprotein levels. This Special Issue of Molecules illustrates the broad impact on biology and medicine of NMR spectroscopy as a tool to investigate biomolecular structure, recognition and dynamics.

Prof. Dr. Brian F. Volkman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • nuclear magnetic resonance
  • protein
  • DNA
  • RNA
  • carbohydrate
  • lipid
  • relaxation
  • chemical shift
  • stable isotope
  • TROSY
  • triple-resonance
  • non-uniform sampling
  • fragment-based screening
  • metabolomics

Published Papers (5 papers)

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Research

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Open AccessArticle Substrate Binding Switches the Conformation at the Lynchpin Site in the Substrate-Binding Domain of Human Hsp70 to Enable Allosteric Interdomain Communication
Molecules 2018, 23(3), 528; https://doi.org/10.3390/molecules23030528
Received: 4 February 2018 / Revised: 18 February 2018 / Accepted: 24 February 2018 / Published: 27 February 2018
Cited by 1 | PDF Full-text (3568 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The stress-induced 70 kDa heat shock protein (Hsp70) functions as a molecular chaperone to maintain protein homeostasis. Hsp70 contains an N-terminal ATPase domain (NBD) and a C-terminal substrate-binding domain (SBD). The SBD is divided into the β subdomain containing the substrate-binding site (βSBD)
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The stress-induced 70 kDa heat shock protein (Hsp70) functions as a molecular chaperone to maintain protein homeostasis. Hsp70 contains an N-terminal ATPase domain (NBD) and a C-terminal substrate-binding domain (SBD). The SBD is divided into the β subdomain containing the substrate-binding site (βSBD) and the α-helical subdomain (αLid) that covers the βSBD. In this report, the solution structures of two different forms of the SBD from human Hsp70 were solved. One structure shows the αLid bound to the substrate-binding site intramolecularly, whereas this intramolecular binding mode is absent in the other structure solved. Structural comparison of the two SBDs from Hsp70 revealed that client-peptide binding rearranges residues at the interdomain contact site, which impairs interdomain contact between the SBD and the NBD. Peptide binding also disrupted the inter-subdomain interaction connecting the αLid to the βSBD, which allows the binding of the αLid to the NBD. The results provide a mechanism for interdomain communication upon substrate binding from the SBD to the NBD via the lynchpin site in the βSBD of human Hsp70. In comparison to the bacterial ortholog, DnaK, some remarkable differences in the allosteric signal propagation among residues within the Hsp70 SBD exist. Full article
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Review

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Open AccessReview Glycosaminoglycan-Protein Interactions by Nuclear Magnetic Resonance (NMR) Spectroscopy
Molecules 2018, 23(9), 2314; https://doi.org/10.3390/molecules23092314
Received: 8 August 2018 / Revised: 29 August 2018 / Accepted: 5 September 2018 / Published: 11 September 2018
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Abstract
Nuclear magnetic resonance (NMR) spectroscopy is one of the most utilized and informative analytical techniques for investigating glycosaminoglycan (GAG)-protein complexes. NMR methods that are commonly applied to GAG-protein systems include chemical shift perturbation, saturation transfer difference, and transferred nuclear Overhauser effect. Although these
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Nuclear magnetic resonance (NMR) spectroscopy is one of the most utilized and informative analytical techniques for investigating glycosaminoglycan (GAG)-protein complexes. NMR methods that are commonly applied to GAG-protein systems include chemical shift perturbation, saturation transfer difference, and transferred nuclear Overhauser effect. Although these NMR methods have revealed valuable insight into the protein-GAG complexes, elucidating high-resolution structural and dynamic information of these often transient interactions remains challenging. In addition, preparation of structurally homogeneous and isotopically enriched GAG ligands for structural investigations continues to be laborious. As a result, understanding of the structure-activity relationship of GAGs is still primitive. To overcome these deficiencies, several innovative NMR techniques have been developed lately. Here, we review some of the commonly used techniques along with more novel methods such as waterLOGSY and experiments to examine structure and dynamic of lysine and arginine side chains to identify GAG-binding sites. We will also present the latest technology that is used to produce isotopically enriched as well as paramagnetically tagged GAG ligands. Recent results that were obtained from solid-state NMR of amyloid’s interaction with GAG are also presented together with a brief discussion on computer assisted modeling of GAG-protein complexes using sparse experimental data. Full article
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Open AccessReview NMR as a Tool to Investigate the Processes of Mitochondrial and Cytosolic Iron-Sulfur Cluster Biosynthesis
Molecules 2018, 23(9), 2213; https://doi.org/10.3390/molecules23092213
Received: 9 July 2018 / Revised: 3 August 2018 / Accepted: 20 August 2018 / Published: 31 August 2018
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Abstract
Iron-sulfur (Fe-S) clusters, the ubiquitous protein cofactors found in all kingdoms of life, perform a myriad of functions including nitrogen fixation, ribosome assembly, DNA repair, mitochondrial respiration, and metabolite catabolism. The biogenesis of Fe-S clusters is a multi-step process that involves the participation
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Iron-sulfur (Fe-S) clusters, the ubiquitous protein cofactors found in all kingdoms of life, perform a myriad of functions including nitrogen fixation, ribosome assembly, DNA repair, mitochondrial respiration, and metabolite catabolism. The biogenesis of Fe-S clusters is a multi-step process that involves the participation of many protein partners. Recent biophysical studies, involving X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry (MS), and small angle X-ray scattering (SAXS), have greatly improved our understanding of these steps. In this review, after describing the biological importance of iron sulfur proteins, we focus on the contributions of NMR spectroscopy has made to our understanding of the structures, dynamics, and interactions of proteins involved in the biosynthesis of Fe-S cluster proteins. Full article
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Open AccessReview A Dynamic Overview of Antimicrobial Peptides and Their Complexes
Molecules 2018, 23(8), 2040; https://doi.org/10.3390/molecules23082040
Received: 20 July 2018 / Revised: 5 August 2018 / Accepted: 9 August 2018 / Published: 15 August 2018
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Abstract
In this narrative review, we comprehensively review the available information about the recognition, structure, and dynamics of antimicrobial peptides (AMPs). Their complex behaviors occur across a wide range of time scales and have been challenging to portray. Recent advances in nuclear magnetic resonance
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In this narrative review, we comprehensively review the available information about the recognition, structure, and dynamics of antimicrobial peptides (AMPs). Their complex behaviors occur across a wide range of time scales and have been challenging to portray. Recent advances in nuclear magnetic resonance and molecular dynamics simulations have revealed the importance of the molecular plasticity of AMPs and their abilities to recognize targets. We also highlight experimental data obtained using nuclear magnetic resonance methodologies, showing that conformational selection is a major mechanism of target interaction in AMP families. Full article
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Open AccessFeature PaperReview Probing Protein-Protein Interactions Using Asymmetric Labeling and Carbonyl-Carbon Selective Heteronuclear NMR Spectroscopy
Molecules 2018, 23(8), 1937; https://doi.org/10.3390/molecules23081937
Received: 10 July 2018 / Revised: 23 July 2018 / Accepted: 25 July 2018 / Published: 3 August 2018
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Abstract
Protein-protein interactions (PPIs) regulate a plethora of cellular processes and NMR spectroscopy has been a leading technique for characterizing them at the atomic resolution. Technically, however, PPIs characterization has been challenging due to multiple samples required to characterize the hot spots at the
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Protein-protein interactions (PPIs) regulate a plethora of cellular processes and NMR spectroscopy has been a leading technique for characterizing them at the atomic resolution. Technically, however, PPIs characterization has been challenging due to multiple samples required to characterize the hot spots at the protein interface. In this paper, we review our recently developed methods that greatly simplify PPI studies, which minimize the number of samples required to fully characterize residues involved in the protein-protein binding interface. This original strategy combines asymmetric labeling of two binding partners and the carbonyl-carbon label selective (CCLS) pulse sequence element implemented into the heteronuclear single quantum correlation (1H-15N HSQC) spectra. The CCLS scheme removes signals of the J-coupled 15N–13C resonances and records simultaneously two individual amide fingerprints for each binding partner. We show the application to the measurements of chemical shift correlations, residual dipolar couplings (RDCs), and paramagnetic relaxation enhancements (PRE). These experiments open an avenue for further modifications of existing experiments facilitating the NMR analysis of PPIs. Full article
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