Article ; Online: Reflections on the catalytic power of a TIM-barrel.
2014 Volume 57, Page(s) 206–212
Abstract: The TIM-barrel fold is described and its propagation throughout the enzyme universe noted ... The functions of the individual front loops of the eponymous TIM-barrel of triosephosphate isomerase are ... of TIM mutants into catalytically active enzymes. The features of the TIM-barrel fold that favor ...
| Abstract | The TIM-barrel fold is described and its propagation throughout the enzyme universe noted. The functions of the individual front loops of the eponymous TIM-barrel of triosephosphate isomerase are presented in a discussion of: (a) electrophilic catalysis, by amino acid side chains from loops 1 and 4, of abstraction of an α-carbonyl hydrogen from substrate dihydroxyacetone phosphate (DHAP) or d-glyceraldehyde 3-phosphate (DGAP). (b) The engineering of loop 3 to give the monomeric variant monoTIM and the structure and catalytic properties of this monomer. (c) The interaction between loops 6, 7 and 8 and the phosphodianion of DHAP or DGAP. (d) The mechanism by which a ligand-gated conformational change, dominated by motion of loops 6 and 7, activates TIM for catalysis of deprotonation of DHAP or DGAP. (e) The conformational plasticity of TIM, and the utilization of substrate binding energy to "mold" the distorted active site loops of TIM mutants into catalytically active enzymes. The features of the TIM-barrel fold that favor effective protein catalysis are discussed. |
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| MeSH term(s) | Amino Acid Sequence ; Animals ; Crystallography, X-Ray ; Enzyme Activation ; Humans ; Models, Molecular ; Molecular Sequence Data ; Mutation ; Protein Conformation ; Triose-Phosphate Isomerase/chemistry ; Triose-Phosphate Isomerase/genetics ; Triose-Phosphate Isomerase/metabolism | |||||
| Chemical Substances | Triose-Phosphate Isomerase (EC 5.3.1.1) | |||||
| Language | English | |||||
| Publishing date | 2014-07-11 | |||||
| Publishing country | United States | |||||
| Document type | Journal Article ; Research Support, N.I.H., Extramural | |||||
| ZDB-ID | 120080-x | |||||
| ISSN | 1090-2120 ; 0045-2068 | |||||
| ISSN (online) | 1090-2120 | |||||
| ISSN | 0045-2068 | |||||
| DOI | 10.1016/j.bioorg.2014.07.001 | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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