Crystal structure of T state aspartate carbamoyltransferase of the hyperthermophilic archaeon **Sulfolobus acidocaldarius**

De Vos, Dirk; Van Petegem, Filip; Remaut, Han; Legrain, Christianne; Glansdorff, Nicolas; Van Beeumen, Jozef J.

doi:10.1016/J.JMB.2004.03.079

Title

Crystal structure of T state aspartate carbamoyltransferase of the hyperthermophilic archaeon **Sulfolobus acidocaldarius**

Author

De Vos, Dirk

Van Petegem, Filip

Remaut, Han

Legrain, Christianne

Glansdorff, Nicolas

Van Beeumen, Jozef J.

Abstract

Aspartate carbamoyltransferase (ATCase) is a model enzyme for understanding allosteric effects. The dodecameric complex exists in two main states (T and R) that differ substantially in their quaternary structure and their affinity for various ligands. Many hypotheses have resulted from the structure of the Escherichia coli ATCase, but so far other crystal structures to test these have been lacking. Here, we present the tertiary and quaternary structure of the T state ATCase of the hyperthermophilic archaeon Sulfolobus acidocaldarius (SaATCT), determined by X-ray crystallography to 2.6 Å resolution. The quaternary structure differs from the E. coli ATCase, by having altered interfaces between the catalytic (C) and regulatory (R) subunits, and the presence of a novel C1R2 type interface. Conformational differences in the 240s loop region of the C chain and the C-terminal region of the R chain affect intersubunit and interdomain interfaces implicated previously in the allosteric behavior of E. coli ATCase. The allosteric-zinc binding domain interface is strengthened at the expense of a weakened R1C4 type interface. The increased hydrophobicity of the C1R1 type interface may stabilize the quaternary structure. Catalytic trimers of the S. acidocaldarius ATCase are unstable due to a drastic weakening of the C1C2 interface. The hyperthermophilic ATCase presents an interesting example of how an allosteric enzyme can adapt to higher temperatures. The structural rearrangement of this thermophilic ATCase may well promote its thermal stability at the expense of changes in the allosteric behavior.

Language

English

Source (journal)

Journal of molecular biology. - London

Publication

London : 2004

ISSN

0022-2836

DOI

10.1016/J.JMB.2004.03.079

10.1016/S0022-2836(04)00379-1

Volume/pages