1AJR

REFINEMENT AND COMPARISON OF THE CRYSTAL STRUCTURES OF PIG CYTOSOLIC ASPARTATE AMINOTRANSFERASE AND ITS COMPLEX WITH 2-METHYLASPARTATE

Summary for 1AJR

• Entry DOI: 10.2210/pdb1ajr/pdb
• Descriptor: ASPARTATE AMINOTRANSFERASE (2 entities in total)
• Functional Keywords: cytosolic aspartate aminotransferase, pig, homodimer in the absence of ligand, aminotransferase
• Biological source: Sus scrofa (pig)
• Cellular location: Cytoplasm: P00503
• Total number of polymer chains: 2
• Total formula weight: 93243.28

Authors

Rhee, S.,Silva, M.M.,Hyde, C.C.,Rogers, P.H.,Metzler, C.M.,Metzler, D.E.,Arnone, A. (deposition date: 1997-05-08, release date: 1997-08-20, Last modification date: 2024-06-05)

Primary citation

Rhee, S.,Silva, M.M.,Hyde, C.C.,Rogers, P.H.,Metzler, C.M.,Metzler, D.E.,Arnone, A.
Refinement and comparisons of the crystal structures of pig cytosolic aspartate aminotransferase and its complex with 2-methylaspartate.
J.Biol.Chem., 272:17293-17302, 1997

PubMed 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.

PubMed: 9211866
DOI: 10.1074/jbc.272.28.17293

Experimental method

X-RAY DIFFRACTION (1.74 Å)