Discovery of novel allosteric effectors based on the predicted allosteric sites for Escherichia coli D-3-phosphoglycerate dehydrogenase.

ABSTRACT: D-3-phosphoglycerate dehydrogenase (PGDH) from Escherichia coli catalyzes the first critical step in serine biosynthesis, and can be allosterically inhibited by serine. In a previous study, we developed a computational method for allosteric site prediction using a coarse-grained two-state Gō Model and perturbation. Two potential allosteric sites were predicted for E. coli PGDH, one close to the active site and the nucleotide binding site (Site I) and the other near the regulatory domain (Site II). In the present study, we discovered allosteric inhibitors and activators based on site I, using a high-throughput virtual screen, and followed by using surface plasmon resonance (SPR) to eliminate false positives. Compounds 1 and 2 demonstrated a low-concentration activation and high-concentratio

SUBMITTER: Wang Q 

PROVIDER: S-EPMC3986399 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature