“Hard Core” Acetyl Coenzyme‐A Carboxylase

Abstract

Diseases involving unregulated cell reproduction, (i.e. cancer) can be inhibited through acetyl coenzyme‐A carboxylase (ACC) manipulation, preventing the lipid production that is imperative for cell survival. ACC catalyzes the first step in the fatty acid biosynthesis. ACC contains two dimers, biotin carboxylase (BC) and carboxyltransferase (CT), and a monomer, biotin carboxyl carrier protein (BCCP). Though BC, CT, and BCCP are separate proteins in prokaryotes, they are linked in a single unit within a eukaryotic cell. BCCP contains two sets of four parallel β sheets and a core of hydrophobic residues, both of which stabilize it. Due to its symmetry BCCP can be described as a capped β sandwich. In fatty‐acid biosynthesis, BCCP oscillates between the BC and CT domains to carboxylate biotin at the N1 site on the BCCD region. The surface of BCCP is interspersed with charged amino acids, arginine and lysine which are positive, and aspartate and glutamine which are negative. BC contains three domains: a central ATP grasp, an N‐terminal and a C‐terminal. The BC dimer works through “half‐site reactivity,” where one subunit binds the substrate with catalysis; another releases the carboxylated biotin product. This Olathe North High School SMART Team (Students Modeling a Research Topic) 3D modeling project is attempting to identify surface charges on BCCP that may contribute to binding of this subunit to BC and CT. Funded by Black & Veatch.