6KJB

wild-type apo-form E. coli ATCase holoenzyme with an unusual open conformation of R167

Replaces:  4WTO

Summary for 6KJB

• Entry DOI: 10.2210/pdb6kjb/pdb
• Descriptor: Aspartate carbamoyltransferase catalytic subunit, Aspartate carbamoyltransferase regulatory chain, ZINC ION, ... (4 entities in total)
• Functional Keywords: aspartate transcarbamoylase holoenzyme, de novo pyrimidine biosynthesis, transferase
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 2
• Total formula weight: 51546.14

Authors

Wang, N.,Lei, Z.,Zheng, J.,Jia, Z.C. (deposition date: 2019-07-22, release date: 2020-06-03, Last modification date: 2023-11-22)

Primary citation

Lei, Z.,Wang, N.,Tan, H.,Zheng, J.,Jia, Z.
Conformational Plasticity of the Active Site Entrance inE. coliAspartate Transcarbamoylase and Its Implication in Feedback Regulation.
Int J Mol Sci, 21:-, 2020

PubMed Abstract: Aspartate transcarbamoylase (ATCase) has been studied for decades and ATCase is referred as a "textbook example" for both feedback regulation and cooperativity. However, several critical questions about the catalytic and regulatory mechanisms of ATCase remain unanswered, especially about its remote feedback regulation. Herein, we determined a structure of ATCase in which a key residue located (Arg167) at the entrance of the active site adopted an uncommon open conformation, representing the first wild-type apo-form ATCase holoenzyme that features this state. Based on the structure and our results of enzymatic characterization, as well as molecular dynamic simulations, we provide new insights into the feedback regulation of ATCase. We speculate that the binding of pyrimidines or purines would affect the hydrogen bond network at the interface of the catalytic and regulatory subunit, which would further influence the stability of the open conformation of Arg167 and the enzymatic activity of ATCase. Our results not only revealed the importance of the previously unappreciated open conformation of Arg167 in the active site, but also helped to provide rationalization for the mechanism of the remote feedback regulation of ATCase.

PubMed: 31947715
DOI: 10.3390/ijms21010320

Experimental method

X-RAY DIFFRACTION (2.06 Å)