2026-09-22T20:56:50Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/84180 2023-07-11 col_2142_5131 col_2142_14789 com_2142_5130 com_2142_14788 com_2142_8903

Luthey-Schulten, Zaida A. Amaro, Rommie E. 2015-09-25T22:13:21Z 2015-09-25T22:13:21Z 10000-01-01 2005 2005 Using traditional and steered molecular dynamics (SMD) simulations, we induced the conduction of ammonia through the (beta/alpha)8 barrel of hisF. Repeated simulations in combination with Jarzynskis identity were used to determine the free energy landscape for ammonia conduction through hisF and showed, for the first time, that it was indeed energetically feasible for this ubiquitous enzymatic fold to exploit its barrel structure to transport reaction intermediates. The architecture of IGP synthase demonstrates remarkable functionality, and we discovered that four conserved residues at the mouth of the barrel act to exclude water while allowing ammonia to pass. We discovered that a conserved network of interactions, present in all known GATs, may serve as a model of allosteric regulation for the entire enzyme family. Through the use of SMD simulations to induce ligand dissociation and additional experimental kinetic assays, we elicited evidence of the allosteric effect in IGP synthase and found a coupled motion between the unbinding of the cyclase ligand and a hinge-opening motion at the interface, which is disrupted when mutations along the conserved allosteric pathway are made. Made available in DSpace on 2015-09-25T22:13:21Z (GMT). No. of bitstreams: 2 license.txt: 4848 bytes, checksum: 96035ab3f5e1c23cc7138a224ce498bd (MD5) 3198918.pdf: 5634248 bytes, checksum: 5fcd5266d2a6fd86abb2bc6663c22d96 (MD5) Previous issue date: 2005 Embargo set by: Seth Robbins for item 85461 Lift date: Forever Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs Restricted to the U of I community idenfinitely during batch ingest of legacy ETDs U of I Only 185 p. Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2005. http://hdl.handle.net/2142/84180 (MiAaPQ)AAI3198918 eng Biophysics, General Investigating the Structure and Function of IGP Synthase text Chemistry Chemistry University of Illinois at Urbana-Champaign Dissertation Ph.D.