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| [[Image:7tim.gif|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_7tim| PDB=7tim | SCENE= }} | | {{STRUCTURE_7tim| PDB=7tim | SCENE= }} |
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| '''STRUCTURE OF THE TRIOSEPHOSPHATE ISOMERASE-PHOSPHOGLYCOLOHYDROXAMATE COMPLEX: AN ANALOGUE OF THE INTERMEDIATE ON THE REACTION PATHWAY'''
| | ===STRUCTURE OF THE TRIOSEPHOSPHATE ISOMERASE-PHOSPHOGLYCOLOHYDROXAMATE COMPLEX: AN ANALOGUE OF THE INTERMEDIATE ON THE REACTION PATHWAY=== |
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| ==Overview==
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| The glycolytic enzyme triosephosphate isomerase (TIM) catalyzes the interconversion of the three-carbon sugars dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde 3-phosphate (GAP) at a rate limited by the diffusion of substrate to the enzyme. We have solved the three-dimensional structure of TIM complexed with a reactive intermediate analogue, phosphoglycolohydroxamate (PGH), at 1.9-A resolution and have refined the structure to an R-factor of 18%. Analysis of the refined structure reveals the geometry of the active-site residues and the interactions they make with the inhibitor and, by analogy, the substrates. The structure is consistent with an acid-base mechanism in which the carboxylate of Glu-165 abstracts a proton from carbon while His-95 donates a proton to oxygen to form an enediol (or enediolate) intermediate. The conformation of the bound substrate stereoelectronically favors proton transfer from substrate carbon to the syn orbital of Glu-165. The crystal structure suggests that His-95 is neutral rather than cationic in the ground state and therefore would have to function as an imidazole acid instead of the usual imidazolium. Lys-12 is oriented so as to polarize the substrate oxygens by hydrogen bonding and/or electrostatic interaction, providing stabilization for the charged transition state. Asn-10 may play a similar role. | | The line below this paragraph, {{ABSTRACT_PUBMED_2043623}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 2043623 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_2043623}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Seaton, B A.]] | | [[Category: Seaton, B A.]] |
| [[Category: Intramolecular oxidoreductase]] | | [[Category: Intramolecular oxidoreductase]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:47:47 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jul 3 15:10:45 2008'' |