title: Solution NMR and computational methods for understanding protein allostery.
abstract: Allosterism is an essential biological regulatory mechanism. In enzymes, allosteric regulation results in an activation or inhibition of catalytic turnover. The mechanisms by which this is accomplished are unclear and vary significantly depending on the enzyme. It is commonly the case that a metabolite binds to the enzyme at a site distant from the catalytic site, yet its binding is coupled to and sensed by the active site. This coupling can manifest in changes in structure, dynamics, or both at the active site. These interactions between the allosteric and active site, which are often quite distant from one another, involve numerous atoms as well as complex conformational rearrangements of the protein secondary and tertiary structure. Interrogation of this complex biological phenomenon necessitates multiple experimental approaches. In this article, we outline a combined solution NMR spectroscopic and computational approach using molecular dynamics and network models to uncover mechanistic aspects of allostery in the enzyme imidazole glycerol phosphate synthase.
authors: Department of Chemistry, Yale University, New Haven, Connecticut 06520, United States.
authors: Gregory
authors: G
authors: Manley
authors: Ivan
authors: I
authors: Rivalta
authors: J Patrick
authors: JP
authors: Loria
mesh_terms: D000494:Allosteric Regulation; D000619:Aminohydrolases / Q000737:chemistry / Q000378:metabolism; D020134:Catalytic Domain; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins; C087227:imidazole glycerol phosphate synthase; D000619:Aminohydrolases