S. Vijayakumar et al., DIFFERENTIAL STABILITY OF BETA-SHEETS AND ALPHA-HELICES IN BETA-LACTAMASE - A HIGH-TEMPERATURE MOLECULAR-DYNAMICS STUDY OF UNFOLDING INTERMEDIATES, Biophysical journal, 65(6), 1993, pp. 2304-2312
Beta-Lactamase, which catalyzes beta-lactam antibiotics, is prototypic
al of large alpha/beta proteins with a scaffolding formed by strong no
ncovalent interactions. Experimentally, the enzyme is well characteriz
ed, and intermediates that are slightly less compact and having nearly
the same content of secondary structure have been identified in the f
olding pathway. In the present study, high temperature molecular dynam
ics simulations have been carried out on the native enzyme in solution
. Analysis of these results in terms of root mean square fluctuations
in cartesian and [phi, psi] space, backbone dihedral angles and second
ary structural hydrogen bonds forms the basis for an investigation of
the topology of partially unfolded states of beta-lactamase. A differe
ntial stability has been observed for alpha-helices and beta-sheets up
on thermal denaturation to putative unfolding intermediates. These obs
ervations contribute to an understanding of the folding/unfolding proc
esses of beta-lactamases in particular, and other alpha/beta proteins
in general.