title: Computational studies of ammonia channel function in glutamine 5'-phosphoribosylpyrophosphate amidotransferase.
abstract: Glutamine 5'-phosphoribosylpyrophosphate amidotransferase (GPATase) catalyzes the synthesis of 5'-phosphoribosylamine in a reaction that involves the translocation of ammonia along an intramolecular tunnel linking the two active sites of the enzyme. We now report a locally enhanced sampling (LES) strategy for modeling ammonia transfer between the active sites of Escherichia coli GPATase in its active conformation. Our calculations demonstrate that the ammonia channel in GPATase is best regarded as a "pipe" through which ammonia travels in the absence of an external "driving" potential. This combined LES/PMF computational approach, which offers a straightforward alternative to steered molecular dynamics simulations in studies of substrate channeling, also provides new insights into the molecular basis of the reduced ammonia transfer efficiency exhibited by the L415A GPATase mutant.
authors.affiliation: Department of Chemistry, University of Florida, Gainesville, Florida 32611-7200, USA.
authors.forename: Xiang S
authors.initials: XS
authors.lastname: Wang
authors.forename: Adrian E
authors.initials: AE
authors.lastname: Roitberg
authors.forename: Nigel G J
authors.initials: NG
authors.lastname: Richards
mesh_terms: D000582:Amidophosphoribosyltransferase / Q000737:chemistry*; D000595:Amino Acid Sequence; D000641:Ammonia / Q000737:chemistry*; D020134:Catalytic Domain; D019295:Computational Biology; D003198:Computer Simulation; D004926:Escherichia coli / Q000737:chemistry / Q000201:enzymology*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding
chemical_list: D029968:Escherichia coli Proteins; D000641:Ammonia; D000582:Amidophosphoribosyltransferase