Allosteric inhibition induces an open WPD-loop: a new avenue towards glioblastoma therapy.

ABSTRACT: The mobility of loops around the catalytic site of a protein remains crucial to its activity. Dynamics of the WPD-loop is an essential determinant of the catalytic activity of tyrosine-protein phosphatase zeta, an implicated protein in glioblastoma cells. The WPD-loop assumes a closed conformation upon substrate binding in order to position its catalytic aspartate to participate in catalysis. Herein, we explore the impact of NAZ2329, a recently identified allosteric inhibitor of tyrosine-protein phosphatase zeta, on the atomic flexibility of the WPD-loop. The druglikeness of NAZ2329 was assessed using the SwissADME online tool. The enzymatic complex was then subjected to conformational simulations using the AMBER molecular dynamics software. Structural analysis revealed that NAZ2329 induce

SUBMITTER: Agoni C 

PROVIDER: S-EPMC9091281 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature