This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
7tim
From Proteopedia
|
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 with PGH as ligand. Active as Triose-phosphate isomerase, with EC number 5.3.1.1 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 Tue Nov 20 15:11:39 2007
