Hybrid Mass Spectrometry Approaches to Determine How L-Histidine Feedback Regulates the Enzyzme MtATP-Phosphoribosyltransferase

Kamila J Pacholarz; Rebecca J Burnley; Thomas A Jowitt; Victoria Ordsmith; João Pedro Pisco; Massimiliano Porrini; Gérald Larrouy-Maumus; Rachel A Garlish; Richard J Taylor; Luiz Pedro Sório de Carvalho; Perdita E Barran

doi:10.1016/j.str.2017.03.005

Hybrid Mass Spectrometry Approaches to Determine How L-Histidine Feedback Regulates the Enzyzme MtATP-Phosphoribosyltransferase

Kamila J Pacholarz, Rebecca J Burnley, Thomas A Jowitt, Victoria Ordsmith, João Pedro Pisco, Massimiliano Porrini, Gérald Larrouy-Maumus, Rachel A Garlish, Richard J Taylor, Luiz Pedro Sório de Carvalho, Perdita E Barran

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Abstract

MtATP-phosphoribosyltransferase (MtATP-PRT) is an enzyme catalyzing the first step of the biosynthesis of L-histidine in Mycobacterium tuberculosis, and proposed to be regulated via an allosteric mechanism. Native mass spectrometry (MS) reveals MtATP-PRT to exist as a hexamer. Conformational changes induced by L-histidine binding and the influence of buffer pH are determined with ion mobility MS, hydrogen deuterium exchange (HDX) MS, and analytical ultracentrifugation. The experimental collision cross-section ((DT)CCSHe) decreases from 76.6 to 73.5 nm(2) upon ligand binding at pH 6.8, which correlates to the decrease in CCS calculated from crystal structures. No such changes in conformation were found at pH 9.0. Further detail on the regions that exhibit conformational change on L-histidine binding is obtained with HDX-MS experiments. On incubation with L-histidine, rapid changes are observed within domain III, and around the active site at longer times, indicating an allosteric effect.

Original language	English
Pages (from-to)	730-738
Number of pages	9
Journal	Structure (London, England : 1993)
Volume	25
Issue number	5
Early online date	6 Apr 2017
DOIs	https://doi.org/10.1016/j.str.2017.03.005
Publication status	Published - 2017

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Manchester Institute of Biotechnology

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Manchester Synthetic Biology Research Centre for Fine and Speciality Chemicals
Scrutton, N. (PI), Azapagic, A. (CoI), Balmer, A. (CoI), Barran, P. (CoI), Breitling, R. (CoI), Delneri, D. (CoI), Dixon, N. (CoI), Faulon, J.-L. (CoI), Flitsch, S. (CoI), Goble, C. (CoI), Goodacre, R. (CoI), Hay, S. (CoI), Kell, D. (CoI), Leys, D. (CoI), Lloyd, J. (CoI), Lockyer, N. (CoI), Martin, P. (CoI), Micklefield, J. (CoI), Munro, A. (CoI), Pedrosa Mendes, P. (CoI), Randles, S. (CoI), Salehi Yazdi, F. (CoI), Shapira, P. (CoI), Takano, E. (CoI), Turner, N. (CoI) & Winterburn, J. (CoI)
14/11/14 → 13/05/20
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Pacholarz, K. J., Burnley, R. J., Jowitt, T. A., Ordsmith, V., Pisco, J. P., Porrini, M., Larrouy-Maumus, G., Garlish, R. A., Taylor, R. J., de Carvalho, L. P. S., & Barran, P. E. (2017). Hybrid Mass Spectrometry Approaches to Determine How L-Histidine Feedback Regulates the Enzyzme MtATP-Phosphoribosyltransferase. Structure (London, England : 1993), 25(5), 730-738. https://doi.org/10.1016/j.str.2017.03.005

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title = "Hybrid Mass Spectrometry Approaches to Determine How L-Histidine Feedback Regulates the Enzyzme MtATP-Phosphoribosyltransferase",

abstract = "MtATP-phosphoribosyltransferase (MtATP-PRT) is an enzyme catalyzing the first step of the biosynthesis of L-histidine in Mycobacterium tuberculosis, and proposed to be regulated via an allosteric mechanism. Native mass spectrometry (MS) reveals MtATP-PRT to exist as a hexamer. Conformational changes induced by L-histidine binding and the influence of buffer pH are determined with ion mobility MS, hydrogen deuterium exchange (HDX) MS, and analytical ultracentrifugation. The experimental collision cross-section ((DT)CCSHe) decreases from 76.6 to 73.5 nm(2) upon ligand binding at pH 6.8, which correlates to the decrease in CCS calculated from crystal structures. No such changes in conformation were found at pH 9.0. Further detail on the regions that exhibit conformational change on L-histidine binding is obtained with HDX-MS experiments. On incubation with L-histidine, rapid changes are observed within domain III, and around the active site at longer times, indicating an allosteric effect.",

keywords = "Journal Article",

author = "Pacholarz, {Kamila J} and Burnley, {Rebecca J} and Jowitt, {Thomas A} and Victoria Ordsmith and Pisco, {Jo{\~a}o Pedro} and Massimiliano Porrini and G{\'e}rald Larrouy-Maumus and Garlish, {Rachel A} and Taylor, {Richard J} and {de Carvalho}, {Luiz Pedro S{\'o}rio} and Barran, {Perdita E}",

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doi = "10.1016/j.str.2017.03.005",

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Pacholarz, KJ, Burnley, RJ, Jowitt, TA, Ordsmith, V, Pisco, JP, Porrini, M, Larrouy-Maumus, G, Garlish, RA, Taylor, RJ, de Carvalho, LPS & Barran, PE 2017, 'Hybrid Mass Spectrometry Approaches to Determine How L-Histidine Feedback Regulates the Enzyzme MtATP-Phosphoribosyltransferase', Structure (London, England : 1993), vol. 25, no. 5, pp. 730-738. https://doi.org/10.1016/j.str.2017.03.005

TY - JOUR

T1 - Hybrid Mass Spectrometry Approaches to Determine How L-Histidine Feedback Regulates the Enzyzme MtATP-Phosphoribosyltransferase

AU - Pacholarz, Kamila J

AU - Burnley, Rebecca J

AU - Jowitt, Thomas A

AU - Ordsmith, Victoria

AU - Pisco, João Pedro

AU - Porrini, Massimiliano

AU - Larrouy-Maumus, Gérald

AU - Garlish, Rachel A

AU - Taylor, Richard J

AU - de Carvalho, Luiz Pedro Sório

AU - Barran, Perdita E

PY - 2017

Y1 - 2017

N2 - MtATP-phosphoribosyltransferase (MtATP-PRT) is an enzyme catalyzing the first step of the biosynthesis of L-histidine in Mycobacterium tuberculosis, and proposed to be regulated via an allosteric mechanism. Native mass spectrometry (MS) reveals MtATP-PRT to exist as a hexamer. Conformational changes induced by L-histidine binding and the influence of buffer pH are determined with ion mobility MS, hydrogen deuterium exchange (HDX) MS, and analytical ultracentrifugation. The experimental collision cross-section ((DT)CCSHe) decreases from 76.6 to 73.5 nm(2) upon ligand binding at pH 6.8, which correlates to the decrease in CCS calculated from crystal structures. No such changes in conformation were found at pH 9.0. Further detail on the regions that exhibit conformational change on L-histidine binding is obtained with HDX-MS experiments. On incubation with L-histidine, rapid changes are observed within domain III, and around the active site at longer times, indicating an allosteric effect.

AB - MtATP-phosphoribosyltransferase (MtATP-PRT) is an enzyme catalyzing the first step of the biosynthesis of L-histidine in Mycobacterium tuberculosis, and proposed to be regulated via an allosteric mechanism. Native mass spectrometry (MS) reveals MtATP-PRT to exist as a hexamer. Conformational changes induced by L-histidine binding and the influence of buffer pH are determined with ion mobility MS, hydrogen deuterium exchange (HDX) MS, and analytical ultracentrifugation. The experimental collision cross-section ((DT)CCSHe) decreases from 76.6 to 73.5 nm(2) upon ligand binding at pH 6.8, which correlates to the decrease in CCS calculated from crystal structures. No such changes in conformation were found at pH 9.0. Further detail on the regions that exhibit conformational change on L-histidine binding is obtained with HDX-MS experiments. On incubation with L-histidine, rapid changes are observed within domain III, and around the active site at longer times, indicating an allosteric effect.

KW - Journal Article

U2 - 10.1016/j.str.2017.03.005

DO - 10.1016/j.str.2017.03.005

M3 - Article

C2 - 28392260

SN - 0969-2126

VL - 25

SP - 730

EP - 738

JO - Structure (London, England : 1993)

JF - Structure (London, England : 1993)

IS - 5

ER -

Hybrid Mass Spectrometry Approaches to Determine How L-Histidine Feedback Regulates the Enzyzme MtATP-Phosphoribosyltransferase

Abstract

Keywords

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UN SDGs

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