Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Mol Biol. 1992 Sep 5;227(1):197-213.

Domain closure in mitochondrial aspartate aminotransferase.

Author information

  • 1Department of Structural Biology, Biozentrum University of Basel, Switzerland.

Abstract

The subunits of the dimeric enzyme aspartate aminotransferase have two domains: one large and one small. The active site lies in a cavity that is close to both the subunit interface and the interface between the two domains. On binding the substrate the domains close together. This closure completely buries the substrate in the active site and moves two arginine side-chains so they form salt bridges with carboxylate groups of the substrate. The salt bridges hold the substrate close to the pyridoxal 5'-phosphate cofactor and in the right position and orientation for the catalysis of the transamination reaction. We describe here the structural changes that produce the domain movements and the closure of the active site. Structural changes occur at the interface between the domains and within the small domain itself. On closure, the core of the small domain rotates by 13 degrees relative to the large domain. Two other regions of the small domain, which form part of the active site, move somewhat differently. A loop, residues 39 to 49, above the active site moves about 1 A less than the core of the small domain. A helix within the small domain forms the "door" of the active site. It moves with the core of the small domain and, in addition, shifts by 1.2 A, rotates by 10 degrees, and switches its first turn from the alpha to the 3(10) conformation. This results in the helix closing the active site. The domain movements are produced by a co-ordinated series of small changes. Within one subunit the polypeptide chain passes twice between the large and small domains. One link involves a peptide in an extended conformation. The second link is in the middle of a long helix that spans both domains. At the interface this helix is kinked and, on closure, the angle of the kink changes to accommodate the movement of the small domain. The interface between the domains is formed by 15 residues in the large domain packing against 12 residues in the small domain and the manner in which these residues pack is essentially the same in the open and closed structures. Domain movements involve changes in the main-chain and side-chain torsion angles in the residues on both sides of the interface. Most of these changes are small; only a few side-chains switch to new conformations.(ABSTRACT TRUNCATED AT 400 WORDS)

PMID:
1522585
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk