The βαβαβ elementary supersecondary structure of the Rossmann fold from porcine lactate dehydrogenase exhibits characteristics of a molten globule

Abstract

Protein classifications show that the Rossmann Fold, which consists of two βαβαβ motifs (BABAB) related by a rough twofold axis, is the most populated αβ fold, and that the βαβ submotif (BAB) is a widespread elementary structural arrangement. Herein, we report MD simulations, circular dichroism and NMR analyses on BAB and BABAB from porcine lactate dehydrogenase to evaluate their intrinsic stability. Our results demonstrate that'BAB is not stable in solution and is not a folding nucleus. We also find that BABAB, despite its appearance of a functional and structural unit, is not an independent and thermodynamically stable folding unit. Rather, we show that BABAB retains most native secondary structure but very little tertiary structure, thus displaying characteristics of a molten globule. © 2005 Wiley-Liss, Inc.