* Senior Investigator: Dennis A. Torchia

* Affiliation: Bone Research Branch, NIDR.

* Research: NMR studies of the structure, interactions, and internal dynamics of proteins in solution, with specific interest in:

* Interactions between inhibitors and enzymes, particularly HlV-protease and S. nuclease.

* Protein-protein interactions, particularly involving TGF-ß1 and its receptor, profilin and actin, and the PTS proteins III GIc and HPr.

* Protein solution structures, particularly TGF-ß1, HIV-1 protease, profilin, and mutants of S. nuclease

* Internal dynamics of proteins, particularly HIV-1 protease, S. nuclease, and profilin

* Personnel/Resources: Sharon Archer (NMR/structural biology); Valerie Copie (NMR/protein structure & dynamics); Linda K. Nicholson (NMR/protein dynamics & structure); Toshi Yamazaki (NMR, protein and peptide structure)

We are well equipped for high-resolution NMR spectroscopy with two Bruker AMX-500 spectrometers available for use. We have three SUN SPARC stations for off-line processing of NMR data, and XPLOR 3.1 is run on a VAX 4000E/500 system in order to derive 3D protein structures from NMR constraints. A Silicon Graphics 4400 work station is available for 3D molecular modeling and structure displays.

* Publications:

J.G. Pelton, D.A. Torchia, N.D. Meadow, & S. Roseman (1993). Protein Sci. 2:543-558. Tautomeric states of the active site histidines of phosphorylated and unphosphorylated III GIc, a signal transducing protein from Escherichia coli, using 2D NMR techniques.

S.J. Archer, V.K. Vinson, T.D. Pollard, & D.A. Torchia (1993). Biochemistry (in press). Secondary structure and topology of acanthamoeba profilin I as determined by NMR spectroscopy.

S.J. Archer, A. Bax, A.B. Roberts, M.B. Sporn, Y. Ogawa, K.A. Piez, J. Weatherbee, M. Tsang, R. Lucas, B. Zheng, J. Wenker, & D.A.Torchia (1993). Biochemistry 32:164-71. Transforming growth factor ß1: secondary structure as determined by heteronuclear magnetic resonance spectroscopy.

L.K. Nicholson, L.E. Kay, D.M. Baldisseri, J. Arango, P.E. Young, A. Bax, & D.A. Torchia (1992). Biochemistry 31:5253-5263. Dynamics of methyl groups in proteins as studied by proton detected 13C NMR spectroscopy. Application to the leucine residues in staphylococcal nuclease.

* Contact: Dr. D. A. Torchia, Bldg. 30, Room 106. NIDR, NIH, Bethesda, MD 20892.

Tel: (301) 496-5750 Fax: (301) 402-0824

E-mail: TORCHIA@YODA.NIDR.NIH.GOV.