7tim
From Proteopedia
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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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[[Category: Ringe, D.]] | [[Category: Ringe, D.]] | ||
[[Category: Seaton, B A.]] | [[Category: Seaton, B A.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 22:47:47 2008'' | |
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Revision as of 19:47, 4 May 2008
STRUCTURE OF THE TRIOSEPHOSPHATE ISOMERASE-PHOSPHOGLYCOLOHYDROXAMATE COMPLEX: AN ANALOGUE OF THE INTERMEDIATE ON THE REACTION PATHWAY
Overview
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.
About this Structure
7TIM is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Structure of the triosephosphate isomerase-phosphoglycolohydroxamate complex: an analogue of the intermediate on the reaction pathway., Davenport RC, Bash PA, Seaton BA, Karplus M, Petsko GA, Ringe D, Biochemistry. 1991 Jun 18;30(24):5821-6. PMID:2043623 Page seeded by OCA on Sun May 4 22:47:47 2008
