Related ArticlesHigh-resolution ex vivo NMR spectroscopy of human Z ?1-antitrypsin.
Nat Commun. 2020 12 11;11(1):6371
Authors: Jagger AM, Waudby CA, Irving JA, Christodoulou J, Lomas DA
Abstract
Genetic mutations predispose the serine protease inhibitor ?1-antitrypsin to misfolding and polymerisation within hepatocytes, causing liver disease and chronic obstructive pulmonary disease. This misfolding occurs via a transiently populated intermediate state, but our structural understanding of this process is limited by the instability of recombinant ?1-antitrypsin variants in solution. Here we apply NMR spectroscopy to patient-derived samples of ?1-antitrypsin at natural isotopic abundance to investigate the consequences of disease-causing mutations, and observe widespread chemical shift perturbations for methyl groups in Z AAT (E342K). By comparison with perturbations induced by binding of a small-molecule inhibitor of misfolding we conclude that they arise from rapid exchange between the native conformation and a well-populated intermediate state. The observation that this intermediate is stabilised by inhibitor binding suggests a paradoxical approach to the targeted treatment of protein misfolding disorders, wherein the stabilisation of disease-associated states provides selectivity while inhibiting further transitions along misfolding pathways.
High-resolution hyperpolarized in vivo metabolic 13C spectroscopy at low magnetic field (48.7mT) following murine tail-vein injection
From The DNP-NMR Blog:
High-resolution hyperpolarized in vivo metabolic 13C spectroscopy at low magnetic field (48.7mT) following murine tail-vein injection
p.p1 {margin: 0.0px 0.0px 0.0px 36.0px; text-indent: -36.0px; font: 12.0px Helvetica}
Coffey, A.M., et al., High-resolution hyperpolarized in vivo metabolic 13C spectroscopy at low magnetic field (48.7mT) following murine tail-vein injection. J. Magn. Reson., 2017. 281(Supplement C): p. 246-252.
http://www.sciencedirect.com/science/article/pii/S1090780717301659
nmrlearner
News from NMR blogs
0
11-18-2017 07:08 AM
[NMR paper] High-Resolution NMR Studies of Human Tissue Factor.
High-Resolution NMR Studies of Human Tissue Factor.
Related Articles High-Resolution NMR Studies of Human Tissue Factor.
PLoS One. 2016;11(9):e0163206
Authors: Nuzzio KM, Watt ED, Boettcher JM, Gajsiewicz JM, Morrissey JH, Rienstra CM
Abstract
In normal hemostasis, the blood clotting cascade is initiated when factor VIIa (fVIIa, other clotting factors are named similarly) binds to the integral membrane protein, human tissue factor (TF). The TF/fVIIa complex in turn activates fX and fIX, eventually concluding with clot formation....
[NMR paper] The three-dimensional high resolution structure of human interferon alpha-2a determin
The three-dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear NMR spectroscopy in solution.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles The three-dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear NMR spectroscopy in solution.
J Mol Biol. 1997 Dec 12;274(4):661-75
Authors: Klaus W, Gsell B, Labhardt AM, Wipf B, Senn H
The solution structure of recombinant human interferon...
nmrlearner
Journal club
0
08-22-2010 05:08 PM
[NMR paper] High-resolution heteronuclear NMR of human ubiquitin in an aqueous liquid crystalline
High-resolution heteronuclear NMR of human ubiquitin in an aqueous liquid crystalline medium.
Related Articles High-resolution heteronuclear NMR of human ubiquitin in an aqueous liquid crystalline medium.
J Biomol NMR. 1997 Oct;10(3):289-92
Authors: Bax A, Tjandra N
A mixture of dihexanoyl phosphatidylcholine and dimyristoyl phosphatidylcholine in water forms disc-shaped particles, often referred to as bicelles . These adopt an ordered, liquid crystalline phase, which can be maintained at very low concentrations of the bicelles (down to 3%...
High-resolution ex vivo NMR spectroscopy of human Z ?1-antitrypsin.
Linear Mode
