How an Inhibitor Bound to Subunit Interface Alters Triosephosphate Isomerase Dynamics.

ABSTRACT: The tunnel region at triosephosphate isomerase (TIM)'s dimer interface, distant from its catalytic site, is a target site for certain benzothiazole derivatives that inhibit TIM's catalytic activity in Trypanosoma cruzi, the parasite that causes Chagas disease. We performed multiple 100-ns molecular-dynamics (MD) simulations and elastic network modeling (ENM) on both apo and complex structures to shed light on the still unclear inhibitory mechanism of one such inhibitor, named bt10. Within the time frame of our MD simulations, we observed stabilization of aromatic clusters at the dimer interface and enhancement of intersubunit hydrogen bonds in the presence of bt10, which point to an allosteric effect rather than destabilization of the dimeric structure. The collective dynamics dictated by

SUBMITTER: Kurkcuoglu Z 

PROVIDER: S-EPMC4576151 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature