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B6db references: 97362209

type Journal Article
authors Rhee, S.; Silva, M. M.; Hyde, C. C.; Rogers, P. H.; Metzler, C. M.; Metzler, D. E.; Arnone, A.
title Refinement and comparisons of the crystal structures of pig cytosolic aspartate aminotransferase and its complex with 2-methylaspartate
journal J Biol Chem
sel unselected
ui 97362209
year (1997)
volume 272
number 28
pages 17293-302.
keywords Acetic Acid/pharmacology
abstract Two high resolution crystal structures of cytosolic aspartate aminotransferase from pig heart provide additional insights into the stereochemical mechanism for ligand-induced conformational changes in this enzyme. Structures of the homodimeric native structure and its complex with the substrate analog 2-methylaspartate have been refined, respectively, with 1.74-A x-ray diffraction data to an R value of 0.170, and with 1.6-A data to an R value of 0.173. In the presence of 2- methylaspartate, one of the subunits (subunit 1) shows a ligand-induced conformational change that involves a large movement of the small domain (residues 12-49 and 327-412) to produce a "closed" conformation. No such transition is observed in the other subunit (subunit 2), because crystal lattice contacts lock it in an "open" conformation like that adopted by subunit 1 in the absence of substrate. By comparing the open and closed forms of cAspAT, we propose a stereochemical mechanism for the open-to-closed transition that involves the electrostatic neutralization of two active site arginine residues by the negative charges of the incoming substrate, a large change in the backbone (phi,psi) conformational angles of two key glycine residues, and the entropy-driven burial of a stretch of hydrophobic residues on the N- terminal helix. The calculated free energy for the burial of this "hydrophobic plug" appears to be sufficient to serve as the driving force for domain closure.
last changed 2007/10/23 14:24

B6db references