Research in this laboratory is centered around solution studies on the structure and dynamics of proteins, protein-protein complexes and protein-nucleic acid complexes using multidimensional NMR spectroscopy, and on the development and application of novel NMR and computational methods to aid in these studies. Particular emphasis is being placed on complexes involved in signal transduction and transcriptional regulation, and on AIDS and AIDS-related proteins. Recent accomplishments include the extension of the applicability of the NMR method to structures larger than 40 kDa. Structures solved in the last year include phosphoryl transfer complexes of enzyme IIA(glucose) + HPr, and enzyme IIA(glucose)enzyme IIB(glucose) of the PTS pathway, ccomplexes of wild-type SRY (the male sex determining factor) and a sex reversal mutant of SRY with DNA, the N-terminal constant region of the nuuclear envelope protein LAP2, and a complex between the KH3 and KH4 domains of FBP and a single stranded DNA 29mer derived from the FUSE element of the cmyc oncogene. Examples of methodological developments include the panoply of 3D and 4D heteronuclear NMR experiments that have been developed at the NIH and are essential for studying larger proteins whose overlapping resonances pose a formidable problem; methods that make use of anisotropy of the alignment tensor (e.g. residual dipolar couplings measured on macromolecules dissolved in dilute liquid crystalline media such as the nematic phases of rod-shaped virus particles) or the diffusion tensor (for highly non-spherical molecules) to provide long-range orientational information that is not available from other NMR parameters that rely entirely on close spatial proximity of atoms; and the development of fast and efficient algorithms for the analysis of NMR spectra and for the computation of three-dimensional structures based on all available experimental NMR restraints. Very recent developments include the use of rigid mody minimization and constrained/restrained simulated annealing to accurately dock protein-protein complexes on the basis of intermolecular NOE and dipolar coupling data.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Intramural Research (Z01)
Project #
1Z01DK029023-11
Application #
6542223
Study Section
(LCP)
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2001
Total Cost
Indirect Cost
Name
U.S. National Inst Diabetes/Digst/Kidney
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Venditti, Vincenzo; Ghirlando, Rodolfo; Clore, G Marius (2013) Structural basis for enzyme I inhibition by ?-ketoglutarate. ACS Chem Biol 8:1232-40
Grishaev, Alexander; Anthis, Nicholas J; Clore, G Marius (2012) Contrast-matched small-angle X-ray scattering from a heavy-atom-labeled protein in structure determination: application to a lead-substituted calmodulin-peptide complex. J Am Chem Soc 134:14686-9
Iwahara, Junji; Tang, Chun; Marius Clore, G (2007) Practical aspects of (1)H transverse paramagnetic relaxation enhancement measurements on macromolecules. J Magn Reson 184:185-95
Clore, G Marius; Tang, Chun; Iwahara, Junji (2007) Elucidating transient macromolecular interactions using paramagnetic relaxation enhancement. Curr Opin Struct Biol 17:603-16
Tang, Chun; Schwieters, Charles D; Clore, G Marius (2007) Open-to-closed transition in apo maltose-binding protein observed by paramagnetic NMR. Nature 449:1078-82
Cai, Mengli; Huang, Ying; Suh, Jeong-Yong et al. (2007) Solution NMR structure of the barrier-to-autointegration factor-Emerin complex. J Biol Chem 282:14525-35
Schwieters, Charles D; Clore, G Marius (2007) A physical picture of atomic motions within the Dickerson DNA dodecamer in solution derived from joint ensemble refinement against NMR and large-angle X-ray scattering data. Biochemistry 46:1152-66
Hu, Kaifeng; Vogeli, Beat; Clore, G Marius (2007) Spin-state selective carbon-detected HNCO with TROSY optimization in all dimensions and double echo-antiecho sensitivity enhancement in both indirect dimensions. J Am Chem Soc 129:5484-91
Suh, Jeong-Yong; Iwahara, Junji; Clore, G Marius (2007) Intramolecular domain-domain association/dissociation and phosphoryl transfer in the mannitol transporter of Escherichia coli are not coupled. Proc Natl Acad Sci U S A 104:3153-8
Iwahara, Junji; Jung, Young-Sang; Clore, G Marius (2007) Heteronuclear NMR spectroscopy for lysine NH(3) groups in proteins: unique effect of water exchange on (15)N transverse relaxation. J Am Chem Soc 129:2971-80

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