Allostery and Evolution: A Molecular Journey Through the Structural and Dynamical Landscape of an Enzyme Super Family.

ABSTRACT: Allosteric regulation is a powerful mechanism for controlling the efficiency of enzymes. Deciphering the evolutionary mechanisms by which allosteric properties have been acquired in enzymes is of fundamental importance. We used the malate (MalDH) and lactate deydrogenases (LDHs) superfamily as model to elucidate this phenomenon. By introducing a few of mutations associated to the emergence of allosteric LDHs into the non-allosteric MalDH from Methanopyrus kandleri, we have gradually shifted its enzymatic profile toward that typical of allosteric LDHs. We first investigated the process triggering homotropic activation. The structures of the resulting mutants show the typical compact organization of the R-active state of LDHs, but a distorted (T-like) catalytic site demonstrating that they c

SUBMITTER: Coquille S 

PROVIDER: S-EPMC11747225 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature