Special Issue "NMR of Proteins and Small Biomolecules"

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A special issue of Molecules (ISSN 1420-3049).

Deadline for manuscript submissions: closed (30 June 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Oliver Zerbe
Institute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland
Website: http://www.oci.uzh.ch/group.pages/zerbe
E-Mail: oliver.zerbe@oci.uzh.ch
Interests: interaction of biomolecules with membranes studied by NMR; structure and dynamics of membrane-associated hormones; structures of G-protein coupled receptors (or their fragments); synthetic models for loops of GPCRs; structure and folding of repeat proteins

Special Issue Information

Dear Colleagues,

NMR is increasingly being used for the study of structure, dynamics and interactions of biomolecules. Accordingly, NMR experiment are frequently used to study peptides, proteins, nuclei acids or carbohydrates. Such studies are frequently conducted in pharmaceutical sciences to optimize small molecules for binding to relevant receptors and begin to play a crucial role in the drug design process. Another particularly exciting field is that we start to understand the correlation of dynamics and function of biomolecules based on NMR studies of internal dynamics.
All previously unpublished manuscripts covering all topics of structure and dynamics including aspects of the drug design process are welcome for this special feature of Molecules. Applications may be from both the solution- or the solid-state NMR field.

Prof. Dr. Oliver Zerbe
Guest Editor

Submission

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. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as 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 refereed through a 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).

Keywords

  • peptide or protein NMR
  • BioNMR
  • protein structure
  • RNA or DNA structure
  • protein dynamics
  • SAR-by-NMR
  • function-dynamics relationship
  • isotope-labelling

Published Papers (23 papers)

Molecules 2014, 19(1), 1353-1366; doi:10.3390/molecules19011353
Received: 12 October 2013; in revised form: 3 January 2014 / Accepted: 16 January 2014 / Published: 22 January 2014
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Molecules 2014, 19(1), 672-685; doi:10.3390/molecules19010672
Received: 24 September 2013; in revised form: 17 December 2013 / Accepted: 18 December 2013 / Published: 7 January 2014
Show/Hide Abstract | Download PDF Full-text (686 KB) | View HTML Full-text | Download XML Full-text |  Supplementary Files

Molecules 2013, 18(11), 14414-14429; doi:10.3390/molecules181114414
Received: 16 October 2013; in revised form: 6 November 2013 / Accepted: 19 November 2013 / Published: 21 November 2013
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Molecules 2013, 18(11), 13410-13424; doi:10.3390/molecules181113410
Received: 21 June 2013; in revised form: 24 October 2013 / Accepted: 27 October 2013 / Published: 30 October 2013
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Molecules 2013, 18(10), 12396-12414; doi:10.3390/molecules181012396
Received: 6 August 2013; in revised form: 26 September 2013 / Accepted: 29 September 2013 / Published: 8 October 2013
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Molecules 2013, 18(10), 11904-11937; doi:10.3390/molecules181011904
Received: 16 July 2013; in revised form: 28 August 2013 / Accepted: 17 September 2013 / Published: 26 September 2013
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Molecules 2013, 18(10), 11873-11903; doi:10.3390/molecules181011873
Received: 30 July 2013; in revised form: 14 September 2013 / Accepted: 16 September 2013 / Published: 26 September 2013
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Molecules 2013, 18(10), 11658-11682; doi:10.3390/molecules181011658
Received: 2 August 2013; in revised form: 17 September 2013 / Accepted: 17 September 2013 / Published: 25 September 2013
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Molecules 2013, 18(9), 11467-11484; doi:10.3390/molecules180911467
Received: 5 August 2013; in revised form: 3 September 2013 / Accepted: 9 September 2013 / Published: 16 September 2013
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Molecules 2013, 18(9), 11311-11326; doi:10.3390/molecules180911311
Received: 17 July 2013; in revised form: 7 September 2013 / Accepted: 10 September 2013 / Published: 13 September 2013
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Molecules 2013, 18(9), 10802-10828; doi:10.3390/molecules180910802
Received: 1 July 2013; in revised form: 19 August 2013 / Accepted: 30 August 2013 / Published: 4 September 2013
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Molecules 2013, 18(9), 10548-10567; doi:10.3390/molecules180910548
Received: 4 July 2013; in revised form: 9 August 2013 / Accepted: 22 August 2013 / Published: 30 August 2013
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Molecules 2013, 18(9), 10162-10188; doi:10.3390/molecules180910162
Received: 23 May 2013; in revised form: 10 August 2013 / Accepted: 13 August 2013 / Published: 22 August 2013
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Molecules 2013, 18(8), 9735-9754; doi:10.3390/molecules18089735
Received: 20 June 2013; in revised form: 31 July 2013 / Accepted: 7 August 2013 / Published: 14 August 2013
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Molecules 2013, 18(8), 9567-9581; doi:10.3390/molecules18089567
Received: 27 June 2013; in revised form: 1 August 2013 / Accepted: 5 August 2013 / Published: 9 August 2013
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Molecules 2013, 18(8), 9451-9476; doi:10.3390/molecules18089451
Received: 27 June 2013; in revised form: 1 August 2013 / Accepted: 5 August 2013 / Published: 7 August 2013
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Molecules 2013, 18(8), 9253-9277; doi:10.3390/molecules18089253
Received: 6 June 2013; in revised form: 27 July 2013 / Accepted: 29 July 2013 / Published: 2 August 2013
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Molecules 2013, 18(8), 9021-9033; doi:10.3390/molecules18089021
Received: 27 June 2013; in revised form: 10 July 2013 / Accepted: 19 July 2013 / Published: 29 July 2013
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Molecules 2013, 18(8), 8906-8918; doi:10.3390/molecules18088906
Received: 14 June 2013; in revised form: 19 July 2013 / Accepted: 22 July 2013 / Published: 26 July 2013
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Molecules 2013, 18(7), 8579-8590; doi:10.3390/molecules18078579
Received: 24 June 2013; in revised form: 18 July 2013 / Accepted: 18 July 2013 / Published: 22 July 2013
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Molecules 2013, 18(7), 7407-7435; doi:10.3390/molecules18077407
Received: 26 April 2013; in revised form: 13 June 2013 / Accepted: 20 June 2013 / Published: 25 June 2013
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Molecules 2013, 18(6), 7103-7119; doi:10.3390/molecules18067103
Received: 20 May 2013; in revised form: 13 June 2013 / Accepted: 14 June 2013 / Published: 18 June 2013
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Molecules 2013, 18(5), 4929-4941; doi:10.3390/molecules18054929
Received: 7 February 2013; in revised form: 19 April 2013 / Accepted: 22 April 2013 / Published: 26 April 2013
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type of Paper: Review
Title: Contributions of NMR to the Understanding of the Coordination Chemistry and DNA Interactions of Metallo-bleomycins
Authors: Teresa Lehmann * and Elena Topchiy
Affiliations: Department of Chemistry, University of Wyoming, Dept 3838, Laramie, WY 82071, USA
Abstract: Bleomycins are a family of glycopeptides antibiotics that have the ability to bind and degrade DNA when bound to key metal ions, which is believed to be responsible for their antitumor activity. Knowledge of the structures of metallo-bleomycins is vital to further characterize their mechanism of action. To this end, numerous structural studies on metallo-bleomycins have been conducted. NMR spectroscopy has had a key role in most of these studies, and has led to very important findings involving metallo-bleomycin-DNA spatial correlations and the coordination chemistry of this important drug. This paper reviews the most important contributions of NMR to the bleomycin field.

Type of Paper: Review
Title: Metabolomics in Pediatric Nephrology
Authors: Vassilios Fanos, Claudia Fanni, Giovanni Ottonello, Antonio Noto, Angelica Dessì and Luigi Atzori
Affiliations: NICU, Puericulture Institute and Neonatal Section and *Department of Toxicology University of Cagliari, Italy
Abstract: Metabolomics, is helping to understand the field of metabolism. Through the rapid characterization of small molecule (metabolites), this new "omics", has the opportunity to explore the interactions such as: genotype-phenotype and genotype-enviromentype, which means it is possible to have a snapshot of the metabolic status, in normal or pathological conditions. At the center of metabolomics is the important concept that an individual's metabolic state is an accurate representation of that individual's state of health or sickness. The latter is also called the 'diseasome. All this forms the basis of personalized or tailored Medicine. In a metabolomic analysis, it is essential to identify two elements: (i) the choice of the biological material (biofluid or tissue) from which to extract the metabolic profile of interest; (ii) the method of investigation:nuclear magnetic resonance (NMR)and mass spectrometry (MS); (iii) statistical evaluation. Traditional markers of acute kidney injury are not sensitive nor specific. Metabolomics is a potential revolution in clinical medicine. Few papers have been published in nephrology and even less in pediatric nephrology. The aim of this review is to make an update on this field underlying present data and future perpectives towards personalized nephrology.

Type of Paper: Review
Title: "NMR Investigations on Metal Interactions with Unstructured Protein Domains"
Authors: De Ricco R., Kozlowski H., Potocki S.and Valensin D.
Affiliations: University of Siena (ITALY), University of Wroclaw, Poland
Abstract: Essential main group (e.g., Na+, Ca2+) and transition metal ions (e.g., Fe2+, Cu2+, Zn2+) play a key role in the structural organization and in the biological function of many macromolecules, like proteins, DNA and RNA. Despite that, healthy conditions require a tight regulation of metal concentrations inside and outside cells since both metal deficiency or overload can lead to cellular dysfunctions. An alter metabolism of transition metal ions (e.g. Cu2+, Zn2+, Ni2+), is implicated in severe and chronic diseases including cancer, neurodegenerative disorders and microbial infection. Nature has developed a sophisticated machinery to balance the content of transition metal ions: many enzymes, transporters and chaperones are involved in these complex processes by controlling metal uptake and delivery to specific cellular domains.
In this scenario many efforts have been directed to clarify metal interactions with amyloidogenic proteins, metal transporters and metal storage proteins by means of different spectroscopic techniques. In this review we describe the NMR approach applied to determine the metal coordination spheres and the structural features of flexible and disordered regions of proteins derived either from metallo-proteins involved in the neurodegenerative processes or from metal chaperons. The investigated systems include (i)copper, iron and zinc binding to unstructured region of Prion Protein, Alpha Synuclein and Amyloid beta; (ii) zinc binding to extracellular domains of ZIP and ZnT metal transporters and (iii) zinc and nickel binding to the loop region of HypA. The NMR behaviors of all these systems is compared and discussed. The benefits and drawbacks of the adopted methodology are also addressed by stressing all the encountered tricks and pitfalls.

Type of Paper: Article
Title:
Application of 13C reductive Methylation of Lysines to Enhance Sensitivity of Conventional NMR Methods
Authors:
Tanmay S. Chavan and Vadim Gaponenko
Affiliations:
Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA
Abstract:
NMR is commonly used to investigate macromolecular interactions.However, sensitivity problems hamper its use for studying such interactions at low physiologically relevant concentrations. At high concentrations, proteins or peptides tend to aggregate. Development of sensitivity enhanced pulse sequence schemes and availability of cryogenic probes significantly lowered the concentration requirements for NMR experiments. Innovative isotope enrichment strategies have potential to further improve the sensitivity of detection of protein-protein interactions by NMR. We propose to increase the sensitivity of conventional NMR techniques by the using 13C reductive methylation of lysines in protein molecules. The rationale for this approach relies on the fact that methyl groups in dimethyl-lysines are degenerate with one 13CH3 signal arising from two carbons and six protons, as compared to one carbon and three protons in aliphatic amino acids. The improved sensitivity allows us to study protein-protein or protein-peptide interactions at very low nanomolar concentrations. We demonstrate the utility of this method by studying the interaction between the post-translationally lapidated hypervariable region of a human proto-oncogenic GTPase K-Ras and a calcium sensor protein Calmodulin. Calmodulin specifically binds K-Ras and modulates its downstream signaling. This binding specificity is attributed to the unique lipidated hypervariable region of K-Ras. At low micromolar concentrations, the post-translationally modified hypervariable region of K-Ras aggregates and binds Calmodulin in a non-specific manner. Hence conventional NMR techniques cannot be used for studying this interaction. Upon reductively methylating the lysines of Calmodulin, we detected signals at physiologically relevant nanomolar concentrations of the lipidated hypervariable region of K-Ras. Thus, we successfully apply the technique of 13C reductive methylation of lysines to enhance the sensitivity of conventional NMR methods.

Type of Paper: Review
Title: Probing Early Misfolding Events in Prion Protein Mutants by NMR Spectroscopy
Authors: Gabriele Giachin and Giuseppe Legname
Affiliations: SISSA, Department of Neuroscience, Via Bonomea 265, I-34136 Trieste, Italy; E-Mail: giachin@sissa.it (G.G.), legname@sissa.it (G.L.)
Abstract: The post-translational conversion of the ubiquitously expressed cellular form of the prion protein, PrPC, into its misfolded and pathogenic isoform, known as prion or PrPSc, plays a key role in prion diseases. These maladies are denoted transmissible spongiform encephalopathies (TSEs) and affect both humans and animals. A prerequisite for understanding TSEs is unraveling the molecular mechanism leading to the conversion process, whereby most α-helical motifs are replaced by β-sheet secondary structures. Importantly, most point mutations linked to inherited prion diseases are clustered in the C-terminal PrPC domain region and cause spontaneous PrPSc conversion. Structural studies with PrP variants promise new clues regarding the proposed conversion mechanism and may help identify “hot spots” in PrPC involved in the pathogenic conversion. These investigations may also shed light on the early structural rearrangements occurring in some PrP epitopes thought to be involved in modulating prion susceptibility. We present a detailed overview of our solution-state NMR studies on prion protein carrying different pathological point mutations and the implications that such findings may have for the future of prion research.

Last update: 22 March 2013

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