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Global folds of proteins with low densities of NOEs using residual dipolar couplings: application to the 370-residue maltodextrin-binding protein.

Publication ,  Journal Article
Mueller, GA; Choy, WY; Yang, D; Forman-Kay, JD; Venters, RA; Kay, LE
Published in: J Mol Biol
June 30, 2000

The global fold of maltose-binding protein in complex with the substrate beta-cyclodextrin was determined by solution NMR methods. The two-domain protein is comprised of a single polypeptide chain of 370 residues, with a molecular mass of 42 kDa. Distance information in the form of H(N)-H(N), H(N)-CH(3) and CH(3)-CH(3) NOEs was recorded on (15)N, (2)H and (15)N, (13)C, (2)H-labeled proteins with methyl protonation in Val, Leu, and Ile (C(delta1) only) residues. Distances to methyl protons, critical for the structure determination, comprised 77 % of the long-range restraints. Initial structures were calculated on the basis of 1943 NOEs, 48 hydrogen bond and 555 dihedral angle restraints. A global pair-wise backbone rmsd of 5.5 A was obtained for these initial structures with rmsd values for the N and C domains of 2.4 and 3.8 A, respectively. Direct refinement against one-bond (1)H(N)-(15)N, (13)C(alpha)-(13)CO, (15)N-(13)CO, two-bond (1)H(N)-(13)CO and three-bond (1)H(N)-(13)C(alpha) dipolar couplings resulted in structures with large numbers of dipolar restraint violations. As an alternative to direct refinement against measured dipolar couplings we have developed an approach where discrete orientations are calculated for each peptide plane on the basis of the dipolar couplings described above. The orientation which best matches that in initial NMR structures calculated from NOE and dihedral angle restraints exclusively is used to refine further the structures using a new module written for CNS. Modeling studies from four different proteins with diverse structural motifs establishes the utility of the methodology. When applied to experimental data recorded on MBP the precision of the family of structures generated improves from 5.5 to 2.2 A, while the rmsd with respect to the X-ray structure (1dmb) is reduced from 5.1 to 3.3 A.

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Published In

J Mol Biol

DOI

ISSN

0022-2836

Publication Date

June 30, 2000

Volume

300

Issue

1

Start / End Page

197 / 212

Location

Netherlands

Related Subject Headings

  • beta-Cyclodextrins
  • Solutions
  • Software
  • Sensitivity and Specificity
  • Protons
  • Protein Folding
  • Protein Conformation
  • Periplasmic Binding Proteins
  • Nuclear Magnetic Resonance, Biomolecular
  • Molecular Weight
 

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Mueller, G. A., Choy, W. Y., Yang, D., Forman-Kay, J. D., Venters, R. A., & Kay, L. E. (2000). Global folds of proteins with low densities of NOEs using residual dipolar couplings: application to the 370-residue maltodextrin-binding protein. J Mol Biol, 300(1), 197–212. https://doi.org/10.1006/jmbi.2000.3842
Mueller, G. A., W. Y. Choy, D. Yang, J. D. Forman-Kay, R. A. Venters, and L. E. Kay. “Global folds of proteins with low densities of NOEs using residual dipolar couplings: application to the 370-residue maltodextrin-binding protein.J Mol Biol 300, no. 1 (June 30, 2000): 197–212. https://doi.org/10.1006/jmbi.2000.3842.
Mueller GA, Choy WY, Yang D, Forman-Kay JD, Venters RA, Kay LE. Global folds of proteins with low densities of NOEs using residual dipolar couplings: application to the 370-residue maltodextrin-binding protein. J Mol Biol. 2000 Jun 30;300(1):197–212.
Mueller, G. A., et al. “Global folds of proteins with low densities of NOEs using residual dipolar couplings: application to the 370-residue maltodextrin-binding protein.J Mol Biol, vol. 300, no. 1, June 2000, pp. 197–212. Pubmed, doi:10.1006/jmbi.2000.3842.
Mueller GA, Choy WY, Yang D, Forman-Kay JD, Venters RA, Kay LE. Global folds of proteins with low densities of NOEs using residual dipolar couplings: application to the 370-residue maltodextrin-binding protein. J Mol Biol. 2000 Jun 30;300(1):197–212.

Published In

J Mol Biol

DOI

ISSN

0022-2836

Publication Date

June 30, 2000

Volume

300

Issue

1

Start / End Page

197 / 212

Location

Netherlands

Related Subject Headings

  • beta-Cyclodextrins
  • Solutions
  • Software
  • Sensitivity and Specificity
  • Protons
  • Protein Folding
  • Protein Conformation
  • Periplasmic Binding Proteins
  • Nuclear Magnetic Resonance, Biomolecular
  • Molecular Weight