Molecular integration of the anti-tropomyosin compound ATM-3507 into the coiled coil overlap region of the cancer-associated Tpm3.1.

ABSTRACT: Tropomyosins (Tpm) determine the functional capacity of actin filaments in an isoform-specific manner. The primary isoform in cancer cells is Tpm3.1 and compounds that target Tpm3.1 show promising results as anti-cancer agents both in vivo and in vitro. We have determined the molecular mechanism of interaction of the lead compound ATM-3507 with Tpm3.1-containing actin filaments. When present during co-polymerization of Tpm3.1 with actin, ³H-ATM-3507 is incorporated into the filaments and saturates at approximately one molecule per Tpm3.1 dimer and with an apparent binding affinity of approximately 2 µM. In contrast, ³H-ATM-3507 is poorly incorporated into preformed Tpm3.1/actin co-polymers. CD spectroscopy and thermal melts using Tpm3.1 peptides containing the C-termi

SUBMITTER: Janco M 

PROVIDER: S-EPMC6677793 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature