Enzyme Structure

Davies, D R.

Abstract

1) Additional inhibitor studies on the aspartyl proteinase from Rhizopus chinensis have been carried out. The inhibitors, analogs of pepstatin, provide information regarding the mechanism of action of this class of enzyme and support the concept of rational drug design based on a knowledge of three-dimensional structure. 2) The structure of the enzyme tryptophan synthase from Salmonella typhimurium has been further studied and partially refined. The enzyme, which is bifunctional with an alpha and beta reaction, is organized in an approximately linear alpha beta beta alpha structure, about 145 A long. The most striking result is the demonstration of the presence of a tunnel linking the two active sites, thus permitting the diffusion of indole, the product of the alpha reaction, to the active site of the beta enzyme.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK034002-25
• Application #: 3917784
• Support Year: 25
• Fiscal Year: 1988

Institution

• Name: U.S. National Inst Diabetes/Digst/Kidney
• Country: United States

Publications

Liu, Lin; Botos, Istvan; Wang, Yan et al. (2008) Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science 320:379-81

Leonard, Joshua N; Ghirlando, Rodolfo; Askins, Janine et al. (2008) The TLR3 signaling complex forms by cooperative receptor dimerization. Proc Natl Acad Sci U S A 105:258-63

Bell, Jessica K; Askins, Janine; Hall, Pamela R et al. (2006) The dsRNA binding site of human Toll-like receptor 3. Proc Natl Acad Sci U S A 103:8792-7

Cohen, Gerson H; Silverton, Enid W; Padlan, Eduardo A et al. (2005) Water molecules in the antibody-antigen interface of the structure of the Fab HyHEL-5-lysozyme complex at 1.7 A resolution: comparison with results from isothermal titration calorimetry. Acta Crystallogr D Biol Crystallogr 61:628-33

Bell, Jessica K; Botos, Istvan; Hall, Pamela R et al. (2005) The molecular structure of the Toll-like receptor 3 ligand-binding domain. Proc Natl Acad Sci U S A 102:10976-80

Bell, Jessica K; Mullen, Gregory E D; Leifer, Cynthia A et al. (2003) Leucine-rich repeats and pathogen recognition in Toll-like receptors. Trends Immunol 24:528-33

Fan, Y X; McPhie, P; Miles, E W (2000) Thermal repair of tryptophan synthase mutations in a regulatory intersubunit salt bridge. Evidence from arrhenius plots, absorption spectra, and primary kinetic isotope effects. J Biol Chem 275:20302-7

Jhee, K H; McPhie, P; Miles, E W (2000) Yeast cystathionine beta-synthase is a pyridoxal phosphate enzyme but, unlike the human enzyme, is not a heme protein. J Biol Chem 275:11541-4

Wolff, E C; Wolff, J; Park, M H (2000) Deoxyhypusine synthase generates and uses bound NADH in a transient hydride transfer mechanism. J Biol Chem 275:9170-7

Miles, E W; Davies, D R (2000) Protein evolution. On the ancestry of barrels. Science 289:1490