Related ArticlesThe tyrosine gate of the bacterial lectin FimH: a conformational analysis by NMR spectroscopy and X-ray crystallography.
Chembiochem. 2015 May 26;16(8):1235-46
Authors: Fiege B, Rabbani S, Preston RC, Jakob RP, Zihlmann P, Schwardt O, Jiang X, Maier T, Ernst B
Abstract
Urinary tract infections caused by uropathogenic E. coli are among the most prevalent infectious diseases. The mannose-specific lectin FimH mediates the adhesion of the bacteria to the urothelium, thus enabling host cell invasion and recurrent infections. An attractive alternative to antibiotic treatment is the development of FimH antagonists that mimic the physiological ligand. A large variety of candidate drugs have been developed and characterized by means of in vitro studies and animal models. Here we present the X-ray co-crystal structures of FimH with members of four antagonist classes. In three of these cases no structural data had previously been available. We used NMR spectroscopy to characterize FimH-antagonist interactions further by chemical shift perturbation. The analysis allowed a clear determination of the conformation of the tyrosine gate motif that is crucial for the interaction with aglycone moieties and was not obvious from X-ray structural data alone. Finally, ITC experiments provided insight into the thermodynamics of antagonist binding. In conjunction with the structural information from X-ray and NMR experiments the results provide a mechanism for the often-observed enthalpy-entropy compensation of FimH antagonists that plays a role in fine-tuning of the interaction.
[NMR paper] Analysis of cytochrome P450 CYP119 ligand-dependent conformational dynamics by two-dimensional NMR and X-ray crystallography.
Analysis of cytochrome P450 CYP119 ligand-dependent conformational dynamics by two-dimensional NMR and X-ray crystallography.
http://www.bionmr.com//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-standard-jbc_final.gif Related Articles Analysis of cytochrome P450 CYP119 ligand-dependent conformational dynamics by two-dimensional NMR and X-ray crystallography.
J Biol Chem. 2015 Apr 17;290(16):10000-17
Authors: Basudhar D, Madrona Y, Kandel S, Lampe JN, Nishida CR, de Montellano PR
...
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06-20-2015 06:44 PM
[NMR paper] An integrative approach combining ion mobility mass spectrometry, X-ray crystallography and NMR spectroscopy to study the conformational dynamics of ?1 -antitrypsin upon ligand binding.
An integrative approach combining ion mobility mass spectrometry, X-ray crystallography and NMR spectroscopy to study the conformational dynamics of ?1 -antitrypsin upon ligand binding.
An integrative approach combining ion mobility mass spectrometry, X-ray crystallography and NMR spectroscopy to study the conformational dynamics of ?1 -antitrypsin upon ligand binding.
Protein Sci. 2015 May 26;
Authors: Nyon MP, Prentice T, Day J, Kirkpatrick J, Sivalingam GN, Levy G, Haq I, Irving JA, Lomas DA, Christodoulou J, Gooptu B, Thalassinos K
...
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05-27-2015 10:39 AM
An integrative approach combining ion mobility mass spectrometry, X-ray crystallography and NMR spectroscopy to study the conformational dynamics of ?1-antitrypsin upon ligand binding
An integrative approach combining ion mobility mass spectrometry, X-ray crystallography and NMR spectroscopy to study the conformational dynamics of ?1-antitrypsin upon ligand binding
Abstract
Native mass spectrometry (MS) methods permit the study of multiple protein species within solution equilibria, whilst ion mobility (IM)-MS can report on conformational behaviour of specific states. We used IM-MS to study a conformationally labile protein (?1-antitrypsin) that undergoes pathological polymerisation in the context of point mutations. The folded, native state of the Z variant remains...
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05-26-2015 08:09 PM
[NMR paper] X-ray crystallography and NMR as tools for the study of protein tyrosine phosphatases.
X-ray crystallography and NMR as tools for the study of protein tyrosine phosphatases.
X-ray crystallography and NMR as tools for the study of protein tyrosine phosphatases.
Methods. 2013 Jul 27;
Authors: Elena Gulerez I, Gehring K
Abstract
Protein tyrosine phosphatases (PTPs) are well recognized as key targets in a wide spectrum of diseases, such as diabetes, obesity and cancer. Their roles in these maladies have been successfully characterized by various methods. However, it is only by utilizing the entire gamut of tools and techniques...
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08-01-2013 12:56 PM
X-ray crystallography and NMR as tools for the study of protein tyrosine phosphatases
X-ray crystallography and NMR as tools for the study of protein tyrosine phosphatases
Publication date: Available online 27 July 2013
Source:Methods</br>
Author(s): Irina Elena Gulerez , Kalle Gehring</br>
Protein tyrosine phosphatases (PTPs) are well recognized as key targets in a wide spectrum of diseases, such as diabetes, obesity and cancer. Their roles in these maladies have been successfully characterized by various methods. However, it is only by utilizing the entire gamut of tools and techniques available that we can build a sufficient knowledge of their...
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07-28-2013 07:11 AM
[NMR paper] Fluorinated Carbohydrates as Lectin Ligands: Dissecting Glycan-Cyanovirin Interactions by Using 19 F NMR Spectroscopy.
Fluorinated Carbohydrates as Lectin Ligands: Dissecting Glycan-Cyanovirin Interactions by Using 19 F NMR Spectroscopy.
Fluorinated Carbohydrates as Lectin Ligands: Dissecting Glycan-Cyanovirin Interactions by Using 19 F NMR Spectroscopy.
Chemistry. 2013 Feb 28;
Authors: Matei E, André S, Glinschert A, Infantino AS, Oscarson S, Gabius HJ, Gronenborn AM
Abstract
NMR spectroscopy and isothermal titration calorimetry (ITC) are powerful methods to investigate ligand-protein interactions. Here, we present a versatile and sensitive fluorine NMR...
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03-01-2013 09:57 PM
Integrated analysis of the conformation of a protein-linked spin label by crystallography, EPR and NMR spectroscopy
Integrated analysis of the conformation of a protein-linked spin label by crystallography, EPR and NMR spectroscopy
Abstract Long-range structural information derived from paramagnetic relaxation enhancement observed in the presence of a paramagnetic nitroxide radical is highly useful for structural characterization of globular, modular and intrinsically disordered proteins, as well as proteinâ??protein and protein-DNA complexes. Here we characterized the conformation of a spin-label attached to the homodimeric protein CylR2 using a combination of X-ray crystallography, electron...
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01-31-2011 06:03 AM
Integrated analysis of the conformation of a protein-linked spin label by crystallography, EPR and NMR spectroscopy.
Integrated analysis of the conformation of a protein-linked spin label by crystallography, EPR and NMR spectroscopy.
Integrated analysis of the conformation of a protein-linked spin label by crystallography, EPR and NMR spectroscopy.
J Biomol NMR. 2011 Jan 28;
Authors: Gruene T, Cho MK, Karyagina I, Kim HY, Grosse C, Giller K, Zweckstetter M, Becker S
Long-range structural information derived from paramagnetic relaxation enhancement observed in the presence of a paramagnetic nitroxide radical is highly useful for structural characterization of...
The tyrosine gate of the bacterial lectin FimH: a conformational analysis by NMR spectroscopy and X-ray crystallography.
Linear Mode
