Enzyme Structure

Davies, D R.

Abstract

The multi-enzyme complex, tryptophan synthase from salmonella typhimurium, has been further analyzed by X-ray diffraction. New very high resolution data have been measured for a mutant of the beta subunit, in the external aldimine form with the amino acids serine and tryptophan, and these structures have been refined. This analysis provides new information about the disposition of residues in the beta active site and their interaction with the intermediates of the beta reaction. Inhibitor complexes of rhizopus pepsin have been analyzed by X-ray diffraction with a view to obtaining more information concerning the mechanism of action. One of these provides a model for the tetrahedral intermediate of the transition state. Examination of the contact distances of this complex provides strong support for the previously proposed mechanism of action. A new method has been presented for the joint refinement of X-ray and NMR data. This method can demonstrate that only very small differences between the structures result from the procedures used, and can highlight real conformational differences caused by physical differences such as crystal packing.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Type: Intramural Research (Z01)
• Project #: 1Z01DK034002-28
• Application #: 3839904
• Support Year: 28
• Fiscal Year: 1992

Institution

• Name: National Institute of Diabetes and Digestive and Kidney Diseases
• 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

Marshall, A D; McPhie, P; Jakoby, W B (2000) Redox control of aryl sulfotransferase specificity. Arch Biochem Biophys 382:95-104

Jhee, K H; Yoshimura, T; Miles, E W et al. (2000) Stereochemistry of the transamination reaction catalyzed by aminodeoxychorismate lyase from Escherichia coli: close relationship between fold type and stereochemistry. J Biochem (Tokyo) 128:679-86

Jhee, K H; McPhie, P; Miles, E W (2000) Domain architecture of the heme-independent yeast cystathionine beta-synthase provides insights into mechanisms of catalysis and regulation. Biochemistry 39:10548-56

Hickman, A B; Li, Y; Mathew, S V et al. (2000) Unexpected structural diversity in DNA recombination: the restriction endonuclease connection. Mol Cell 5:1025-34