1EKX

THE ISOLATED, UNREGULATED CATALYTIC TRIMER OF ASPARTATE TRANSCARBAMOYLASE COMPLEXED WITH BISUBSTRATE ANALOG PALA (N-(PHOSPHONACETYL)-L-ASPARTATE)

1EKX の概要

• エントリーDOI: 10.2210/pdb1ekx/pdb
• 関連するPDBエントリー: 3CSU
• 分子名称: ASPARTATE TRANSCARBAMOYLASE, N-(PHOSPHONACETYL)-L-ASPARTIC ACID, CALCIUM ION, ... (4 entities in total)
• 機能のキーワード: atcase catalytic subunit, bisubstrate analog complex, transferase
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 104250.42

構造登録者

Endrizzi, J.A.,Beernink, P.T.,Alber, T.,Schachman, H.K. (登録日: 2000-03-09, 公開日: 2000-05-12, 最終更新日: 2024-02-07)

主引用文献

Endrizzi, J.A.,Beernink, P.T.,Alber, T.,Schachman, H.K.
Binding of bisubstrate analog promotes large structural changes in the unregulated catalytic trimer of aspartate transcarbamoylase: implications for allosteric regulation induced cell migration.
Proc.Natl.Acad.Sci.USA, 97:5077-5082, 2000

PubMed Abstract: A central problem in understanding enzyme regulation is to define the conformational states that account for allosteric changes in catalytic activity. For Escherichia coli aspartate transcarbamoylase (ATCase; EC) the active, relaxed (R state) holoenzyme is generally assumed to be represented by the crystal structure of the complex of the holoenzyme with the bisubstrate analog N-phosphonacetyl-L-aspartate (PALA). It is unclear, however, which conformational differences between the unliganded, inactive, taut (T state) holoenzyme and the PALA complex are attributable to localized effects of inhibitor binding as contrasted to the allosteric transition. To define the conformational changes in the isolated, nonallosteric C trimer resulting from the binding of PALA, we determined the 1.95-A resolution crystal structure of the C trimer-PALA complex. In contrast to the free C trimer, the PALA-bound trimer exhibits approximate threefold symmetry. Conformational changes in the C trimer upon PALA binding include ordering of two active site loops and closure of the hinge relating the N- and C-terminal domains. The C trimer-PALA structure closely resembles the liganded C subunits in the PALA-bound holoenzyme. This similarity suggests that the pronounced hinge closure and other changes promoted by PALA binding to the holoenzyme are stabilized by ligand binding. Consequently, the conformational changes attributable to the allosteric transition of the holoenzyme remain to be defined.

PubMed: 10805770
DOI: 10.1073/pnas.090087197

実験手法

X-RAY DIFFRACTION (1.95 Å)