Steitz

J. Rebek, Jr., (1987) first developed a new synthesis of Kemp s acid and then extensively explored its application in model studies. The synthesis involves the straightforward hydrogenation (A. Steitz, 1968), esterification and methylation of inexpensive 1,3,5-benzenetricar-boxylic acid (trimesic acid 30/100 g). The methylation of the trimethyl ester with dimethyl sulfate, mediated by lithium diisopropylamide (V. J. Shiner, 1981), produced mainly the desired aff-cis-1,3,5-trimethyl isomer, which was saponified to give Kemp s acid. 

The stmcture was determined to 2.8 A resolution in the laboratory of Tom Steitz, Yale University, (d) The glycolytic enzyme phospho-glycerate mutase, which catalyzes transfer of a phos-phoryl group from carbon 3 to carbon 2 In phosphoglycerate. The structure was determined to 2.S A resolution in the laboratory of Herman Watson, Bristol University, UK. (Adapted from J. Richardson.)... 

Goldman, A., Ollis, D.L., Steitz, T.A. Crystal structure of muconate lactonizing enzyme at 3 A resolution. 

Steitz, T.A., et al. High resolution x-ray structure of yeast hexokinase, an allosteric protein exhibiting a non-symmetric arrangement of subunits. 

Many biochemical and biophysical studies of CAP-DNA complexes in solution have demonstrated that CAP induces a sharp bend in DNA upon binding. This was confirmed when the group of Thomas Steitz at Yale University determined the crystal structure of cyclic AMP-DNA complex to 3 A resolution. The CAP molecule comprises two identical polypeptide chains of 209 amino acid residues (Figure 8.24). Each chain is folded into two domains that have separate functions (Figure 8.24b). The larger N-terminal domain binds the allosteric effector molecule, cyclic AMP, and provides all the subunit interactions that form the dimer. The C-terminal domain contains the helix-tum-helix motif that binds DNA. 

Steitz has suggested that DNA bending by CAP could contribute to activation of transcription by looping the DNA around CAP to provide for contacts between RNA polymerase and DNA upstream of the CAP-binding site. Such a model could explain how CAP can activate transcription from a variety of distances from the RNA polymerase-binding site since the size of the loop could vary. 

Steitz, T.A. Stmctural studies of protein-nucleic acid interaction the sources of sequence-specific binding. 

Weber, L, Steitz, T.A. The structure of a complex of catabo-lite gene activator protein and cyclic AMP refined at 2.S A resolution. /. Mol. Biol. 198 311-326, 1987. 

Steitz, T, and Shulman, R., 1982. Cry.stallographic and NMR. studies of the serine proteases. Annual Review of Biophysics and Bioengineering 4.4.4.. 

The successful use of these X-ray crysallographic techniques in studying the enzyme-substrate interactions of lysozyme (21) and chymotrypsin (22) has recently been reviewed by Blow and Steitz (16) and Blow (23). To date, however, these methods have had only limited application, since the detailed structures of only about ten enzymes have been elucidated by X-ray diffraction... 

The structure of the ribosome s large subunit has recently been resolved at 2.4-A resolution by means of x-ray crystallography N Ban, P Nissen, J Hansen, PB Moore, TA Steitz. Science... 

The atomic structure of this subunit and its complexes with substrate analogs revealed the enzymatic activity of the rRNA backbone. Thus, the ribosome is in fact a ribozyme P Nissen, J Hansen, N Ban, PB Moore, TA Steitz. Science 289 920-930, 2000. Atomic structure of the ribosome s small 30S subunit, resolved at 5 A WM Clemons Jr, JL May, BT Wimberly, JP McCutcheon, MS Capel, V Ramakrishnan. Nature 400 833-840, 1999. The 8-A crystal structure of the 70S ribosome reveals a double-helical RNA bridge between the 50S and the 30S subunit GM Culver, JH Cate, GZ Yusupova, MM Yusupov, HF Noller. Science 285 2133-2136, 1999. 

Examples (a) nucleosome K Huger, AW Mader, RK Richmond, DF Sargent, TJ Richmond. Nature 389 251-260, 1997 (b) DNA polymerases CA Brautigam, TA Steitz. Curr. Opin. Struct. Biol. 8 54-63, 1998 (c) single-stranded binding protein Y Shamoo, AM Friedman, MR Parsons, WH Konigsberg, TA Steitz. Nature 376 362-366, 1995 (d) restriction endonucleases RA Kovall, BW Matthews. Curr. Opin. Chem. Biol. 3 578-583, 1999 (e) DNA lig-ase S Shuman. Structure 4 653-656, 1996 (f) DNA helicases MC Hall, SW Matson. Mol. Microbiol. 34 867-877, 1999 (g) zinc-finger proteins Y Choo, JW Schwabe. Nat. Struct. Biol. 5 253-255, 1998. 

Dai Q, Choy E, Chiu V, Romano J, Slivka SR, Steitz SA, Michaelis S, Philips MR (1998) Journal of Biological Chemistry 273 15,030... 

---