Analysis of the low-frequency normal modes of the R state of aspartate transcarbamylase and a comparison with the T state modes.
Aspartate transcarbamylase (ATCase) is a classic example of an allosteric enzyme. It catalyzes the conversion of aspartate to carbamyl aspartate, which is the first substrate in the biosynthesis of pyrimidines. Although ATCase is well characterized, both structurally and biochemically, little is known at the atomic level about the large amplitude motions that govern its T-->R quaternary transition. We present the results of calculations of the very-low-frequency normal modes of the CTP-ligated R state ATCase, and we compare them with the equivalent modes in the CTP-ligated T state ATCase. The large-amplitude, delocalized modes of frequencies below 4 cm-1 contribute a large fraction of the atomic fluctuations observed experimentally. They show some ability to drive the R-state structure towards the T-state structure, by promoting some of the quaternary structure rearrangements that take place during the allosteric process. Their potential role in the T-->R transition is quantified and compared with the role of the low-frequency modes of the T state in the quaternary rearrangement.
Thomas
A
A
Laboratoire de Dynamique Moléculaire, Institut de Biologie Structurale-Jean-Pierre Ebel, Grenoble, France.
Field
M J
MJ
Perahia
D
D
D000494:Allosteric Regulation; D001221:Aspartate Carbamoyltransferase / Q000737:chemistry*; D008958:Models, Molecular
D001221:Aspartate Carbamoyltransferase