Discovery and Characterization of Antibody Probes of Module 2 of the 6-Deoxyerythronolide B Synthase.

ABSTRACT: Fragment antigen-binding domains of antibodies (F_abs) are powerful probes of structure-function relationships of assembly line polyketide synthases (PKSs). We report the discovery and characterization of F_abs interrogating the structure and function of the ketosynthase-acyltransferase (KS-AT) core of Module 2 of the 6-deoxyerythronolide B synthase (DEBS). Two F_abs (AC2 and BB1) were identified to potently inhibit the catalytic activity of Module 2. Both AC2 and BB1 were found to modulate ACP-mediated reactions catalyzed by this module, albeit by distinct mechanisms. AC2 primarily affects the rate (k_cat), whereas BB1 increases the K_M of an ACP-mediated reaction. A third F_ab, AA5, binds to the KS-AT fragment of D

SUBMITTER: Guzman KM 

PROVIDER: S-EPMC10274564 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature