Attilio Di Pietro
France
Research Article
Nucleotide-free Crystal Structure of Nucleotide-binding Domain 1 from Human ABCC1 Supports a ‘General-Base Catalysis’ Mechanism for ATP Hydrolysis
Author(s): Vincent Chaptal, Sandrine Magnard, Virginie Gueguen-Chaignon, Pierre Falson, Attilio Di Pietro and Hélène Baubichon-CortayVincent Chaptal, Sandrine Magnard, Virginie Gueguen-Chaignon, Pierre Falson, Attilio Di Pietro and Hélène Baubichon-Cortay
ATP-binding cassette (ABC) transporters are molecular motors that transport substrates through biological membranes, using the energy of ATP binding and hydrolysis to foster a series of conformational changes that follow the alternating access mechanism principles. While this general scheme of substrate transport is well accepted, details about the ATP hydrolysis mechanism itself are still a matter of debate. Decades of biochemical and structural studies have identified well-conserved key residues involved in the enzymatic reaction, but their actual role, or order in the hydrolytic process, differ according to the mechanism involved. Here, we investigate the fundamental mechanisms of ATP hydrolysis, by reporting the nucleotide-free structure of the N-terminal nucleotide-Binding Domain (NBD1) of human Multidrug Resistance Protein 1 (MRP1/ABCC1), a transporter of chemotherapeutic drugs... View More»
