Glutamine Hydrolysis by Imidazole Glycerol Phosphate Synthase Displays Temperature Dependent Allosteric Activation

Frontiers in Molecular Biosciences
George P LisiJ Patrick Loria

Abstract

The enzyme imidazole glycerol phosphate synthase (IGPS) is a model for studies of long-range allosteric regulation in enzymes. Binding of the allosteric effector ligand N'-[5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide-ribonucleotide (PRFAR) stimulates millisecond (ms) timescale motions in IGPS that enhance its catalytic function. We studied the effect of temperature on these critical conformational motions and the catalytic mechanism of IGPS from the hyperthermophile Thermatoga maritima in an effort to understand temperature-dependent allostery. Enzyme kinetic and NMR dynamics measurements show that apo and PRFAR-activated IGPS respond differently to changes in temperature. Multiple-quantum Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion experiments performed at 303, 323, and 343 K (30, 50, and 70°C) reveal that millisecond flexibility is enhanced to a higher degree in apo IGPS than in the PRFAR-bound enzyme as the sample temperature is raised. We find that the flexibility of the apo enzyme is nearly identical to that of its PRFAR activated state at 343 K, whereas conformational motions are considerably different between these two forms of the enzyme at room temperature. Arrhenius analyses of these flexi...Continue Reading

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Citations

Jul 10, 2020·Protein Science : a Publication of the Protein Society·Yvonne H ChanCharles R Matthews
Jul 8, 2019·Journal of Biomolecular NMR·Jared RovnySean E Barrett
Jul 29, 2021·Journal of Structural Biology·Vitor Medeiros AlmeidaSandro Roberto Marana
Nov 27, 2018·Biochemistry·Teresa F G MachadoRafael G da Silva
Apr 7, 2020·Journal of Chemical Theory and Computation·Peter T LakeMartin McCullagh
Dec 6, 2021·Biophysical Journal·Federica MaschiettoIvan Rivalta

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Methods Mentioned

BETA
NMR
circular dichroism
isothermal titration calorimetry
chemical exchange

Software Mentioned

GraphPad
GraphPad Prism
SPARKY
NMRPipe

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