Journal article

Modifying the resolving cysteine affects the structure and hydrogen peroxide reactivity of peroxiredoxin 2

Alexander Peskin, Flavia C Meotti, Kelsey M Kean, Christoph Gobl, Albert Souza Peixoto, Paul E Pace, Christopher R Horne, Sarah G Heath, Jennifer M Crowther, Renwick CJ Dobson, P Andrew Karplus, Christine C Winterbourn

JOURNAL OF BIOLOGICAL CHEMISTRY | ELSEVIER | Published : 2021

Abstract

Peroxiredoxin 2 (Prdx2) is a thiol peroxidase with an active site Cys (C52) that reacts rapidly with H2O2 and other peroxides. The sulfenic acid product condenses with the resolving Cys (C172) to form a disulfide which is recycled by thioredoxin or GSH via mixed disulfide intermediates or undergoes hyperoxidation to the sulfinic acid. C172 lies near the C terminus, outside the active site. It is not established whether structural changes in this region, such as mixed disulfide formation, affect H2O2 reactivity. To investigate, we designed mutants to cause minimal (C172S) or substantial (C172D and C172W) structural disruption. Stopped flow kinetics and mass spectrometry showed that mutation t..

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Grants

Awarded by US National Institutes of Health


Awarded by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)


Awarded by Office of Science, Office of Basic Energy Sciences, of the US Department of Energy


Funding Acknowledgements

This work was supported by the Marsden Fund of New Zealand (C. C. W., A. V. P., P. E. P.); by the US National Institutes of Health (grant R01-GM119227 to P. A. K. and K12-GM000678 to K. M. K.); by a Sir Charles Hercus Fellowship from the Health Research Council of New Zealand (C. G.), the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) projects: CEPID-Redoxoma 2013/07937-8, Young Investigator 2018/14898-2 and multi-user equipment 2015/10411-3 grants (Brazil, FM). The Advanced Light Source is supported by the Director, Office of Science, Office of Basic Energy Sciences, of the US Department of Energy under Contract No. DE-AC0205CH11231. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.