title: H-loop histidine catalyzes ATP hydrolysis in the E. coli ABC-transporter HlyB.
abstract: Adenosine triphosphate (ATP)-binding cassette (ABC) transporters form a family of molecular motor proteins that couple ATP hydrolysis to substrate translocation across cell membranes. Each nucleotide binding domain of ABC-transporters contains a highly conserved H-loop histidine residue, whose precise mechanistic role in motor functions has remained elusive. By using combined quantum mechanical and molecular mechanical (QM/MM) calculations, we showed that the conserved H-loop residue H662 in E. coli HlyB, a bacterial ABC-transporter, can act first as a general acid and then as a general base to facilitate proton transfer in ATP hydrolysis. Without the assistance of H662, direct proton transfer from the lytic water to ATP results in a substantially higher barrier height. Our findings suggest that the essential function of the H-loop residue H662 is to provide a "chemical linchpin" that shuttles protons between reactants through a relay mechanism, thereby catalyzing ATP hydrolysis in HlyB.
authors: Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, 402 N. Blackford St., Indianapolis, IN 46202, USA. jpu@iupui.edu.
authors: Yan
authors: Y
authors: Zhou
authors: Pedro
authors: P
authors: Ojeda-May
authors: Jingzhi
authors: J
authors: Pu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000378:metabolism*; D055162:Biocatalysis; D002352:Carrier Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D006460:Hemolysin Proteins / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism*; D006868:Hydrolysis; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D006460:Hemolysin Proteins; C050837:Hlyb protein, Bacteria; D006639:Histidine; D000255:Adenosine Triphosphate