Molecular dynamics simulations and rigid body (TLS) analysis of aspartate carbamoyltransferase: evidence for an uncoupled R state.
In the R form of ATCase complexed with the bisubstrate analogue, N-(phosphonacetyl)-L-aspartate, large temperature factors are reported for the allosteric domains of the regulatory chains. We studied the conformational flexibility of the holoenzyme with molecular dynamics simulations and rigid body (TLS) analysis. The results of the molecular dynamics simulations suggest that, although local atomic fluctuations account for the temperature factors of the catalytic and zinc domains, they do not account for the large temperature factors of the allosteric regions. However, the temperature factors of the allosteric domains can be satisfactorily analyzed using a rigid body model. The simulations and rigid body analysis support the idea that the allosteric regions are mechanically uncoupled from the rest of the enzyme in the PALA structure. Implications of this uncoupling for allosteric regulation are discussed.
Tanner
J J
JJ
Department of Biochemistry and Biophysical Sciences, University of Houston, Texas 77204-5934.
Smith
P E
PE
Krause
K L
KL
D000495:Allosteric Site; D001221:Aspartate Carbamoyltransferase / Q000737:chemistry*; D003198:Computer Simulation; D003460:Crystallization; D004926:Escherichia coli / Q000201:enzymology; D015394:Molecular Structure; D011487:Protein Conformation; D013816:Thermodynamics
D001221:Aspartate Carbamoyltransferase