Cargando…
Improved Cross Validation of a Static Ubiquitin Structure Derived from High Precision Residual Dipolar Couplings Measured in a Drug-Based Liquid Crystalline Phase
[Image: see text] The antibiotic squalamine forms a lyotropic liquid crystal at very low concentrations in water (0.3-3.5% w/v), which remains stable over a wide range of temperature (1-40 °C) and pH (4-8). Squalamine is positively charged, and comparison of the alignment of ubiquitin relative to 36...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2014
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954408/ https://www.ncbi.nlm.nih.gov/pubmed/24568736 http://dx.doi.org/10.1021/ja4132642 |
_version_ | 1782307475826933760 |
---|---|
author | Maltsev, Alexander S. Grishaev, Alexander Roche, Julien Zasloff, Michael Bax, Ad |
author_facet | Maltsev, Alexander S. Grishaev, Alexander Roche, Julien Zasloff, Michael Bax, Ad |
author_sort | Maltsev, Alexander S. |
collection | PubMed |
description | [Image: see text] The antibiotic squalamine forms a lyotropic liquid crystal at very low concentrations in water (0.3-3.5% w/v), which remains stable over a wide range of temperature (1-40 °C) and pH (4-8). Squalamine is positively charged, and comparison of the alignment of ubiquitin relative to 36 previously reported alignment conditions shows that it differs substantially from most of these, but is closest to liquid crystalline cetyl pyridinium bromide. High precision residual dipolar couplings (RDCs) measured for the backbone (1)H-(15)N, (15)N-(13)C′, (1)H(α)-(13)C(α), and (13)C′-(13)C(α) one-bond interactions in the squalamine medium fit well to the static structural model previously derived from NMR data. Inclusion into the structure refinement procedure of these RDCs, together with (1)H-(15)N and (1)H(α)-(13)C(α) RDCs newly measured in Pf1, results in improved agreement between alignment-induced changes in (13)C′ chemical shift, (3)J(HNHα) values, and (13)C(α)-(13)C(β) RDCs and corresponding values predicted by the structure, thereby validating the high quality of the single-conformer structural model. This result indicates that fitting of a single model to experimental data provides a better description of the average conformation than does averaging over previously reported NMR-derived ensemble representations. The latter can capture dynamic aspects of a protein, thus making the two representations valuable complements to one another. |
format | Online Article Text |
id | pubmed-3954408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-39544082014-03-18 Improved Cross Validation of a Static Ubiquitin Structure Derived from High Precision Residual Dipolar Couplings Measured in a Drug-Based Liquid Crystalline Phase Maltsev, Alexander S. Grishaev, Alexander Roche, Julien Zasloff, Michael Bax, Ad J Am Chem Soc [Image: see text] The antibiotic squalamine forms a lyotropic liquid crystal at very low concentrations in water (0.3-3.5% w/v), which remains stable over a wide range of temperature (1-40 °C) and pH (4-8). Squalamine is positively charged, and comparison of the alignment of ubiquitin relative to 36 previously reported alignment conditions shows that it differs substantially from most of these, but is closest to liquid crystalline cetyl pyridinium bromide. High precision residual dipolar couplings (RDCs) measured for the backbone (1)H-(15)N, (15)N-(13)C′, (1)H(α)-(13)C(α), and (13)C′-(13)C(α) one-bond interactions in the squalamine medium fit well to the static structural model previously derived from NMR data. Inclusion into the structure refinement procedure of these RDCs, together with (1)H-(15)N and (1)H(α)-(13)C(α) RDCs newly measured in Pf1, results in improved agreement between alignment-induced changes in (13)C′ chemical shift, (3)J(HNHα) values, and (13)C(α)-(13)C(β) RDCs and corresponding values predicted by the structure, thereby validating the high quality of the single-conformer structural model. This result indicates that fitting of a single model to experimental data provides a better description of the average conformation than does averaging over previously reported NMR-derived ensemble representations. The latter can capture dynamic aspects of a protein, thus making the two representations valuable complements to one another. American Chemical Society 2014-02-25 2014-03-12 /pmc/articles/PMC3954408/ /pubmed/24568736 http://dx.doi.org/10.1021/ja4132642 Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) |
spellingShingle | Maltsev, Alexander S. Grishaev, Alexander Roche, Julien Zasloff, Michael Bax, Ad Improved Cross Validation of a Static Ubiquitin Structure Derived from High Precision Residual Dipolar Couplings Measured in a Drug-Based Liquid Crystalline Phase |
title | Improved
Cross Validation of a Static Ubiquitin Structure
Derived from High Precision Residual Dipolar Couplings Measured in
a Drug-Based Liquid Crystalline Phase |
title_full | Improved
Cross Validation of a Static Ubiquitin Structure
Derived from High Precision Residual Dipolar Couplings Measured in
a Drug-Based Liquid Crystalline Phase |
title_fullStr | Improved
Cross Validation of a Static Ubiquitin Structure
Derived from High Precision Residual Dipolar Couplings Measured in
a Drug-Based Liquid Crystalline Phase |
title_full_unstemmed | Improved
Cross Validation of a Static Ubiquitin Structure
Derived from High Precision Residual Dipolar Couplings Measured in
a Drug-Based Liquid Crystalline Phase |
title_short | Improved
Cross Validation of a Static Ubiquitin Structure
Derived from High Precision Residual Dipolar Couplings Measured in
a Drug-Based Liquid Crystalline Phase |
title_sort | improved
cross validation of a static ubiquitin structure
derived from high precision residual dipolar couplings measured in
a drug-based liquid crystalline phase |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3954408/ https://www.ncbi.nlm.nih.gov/pubmed/24568736 http://dx.doi.org/10.1021/ja4132642 |
work_keys_str_mv | AT maltsevalexanders improvedcrossvalidationofastaticubiquitinstructurederivedfromhighprecisionresidualdipolarcouplingsmeasuredinadrugbasedliquidcrystallinephase AT grishaevalexander improvedcrossvalidationofastaticubiquitinstructurederivedfromhighprecisionresidualdipolarcouplingsmeasuredinadrugbasedliquidcrystallinephase AT rochejulien improvedcrossvalidationofastaticubiquitinstructurederivedfromhighprecisionresidualdipolarcouplingsmeasuredinadrugbasedliquidcrystallinephase AT zasloffmichael improvedcrossvalidationofastaticubiquitinstructurederivedfromhighprecisionresidualdipolarcouplingsmeasuredinadrugbasedliquidcrystallinephase AT baxad improvedcrossvalidationofastaticubiquitinstructurederivedfromhighprecisionresidualdipolarcouplingsmeasuredinadrugbasedliquidcrystallinephase |