Structural insights on the efficient catalysis of hydroperoxide reduction by Ohr: Crystallographic and molecular dynamics approaches

PloS One
Erika PiccirilloAntonia T-do Amaral

Abstract

Organic hydroperoxide resistance (Ohr) enzymes are highly efficient Cys-based peroxidases that play central roles in bacterial response to fatty acid hydroperoxides and peroxynitrite, two oxidants that are generated during host-pathogen interactions. In the active site of Ohr proteins, the conserved Arg (Arg19 in Ohr from Xylella fastidiosa) and Glu (Glu51 in Ohr from Xylella fastidiosa) residues, among other factors, are involved in the extremely high reactivity of the peroxidatic Cys (Cp) toward hydroperoxides. In the closed state, the thiolate of Cp is in close proximity to the guanidinium group of Arg19. Ohr enzymes can also assume an open state, where the loop containing the catalytic Arg is far away from Cp and Glu51. Here, we aimed to gain insights into the putative structural switches of the Ohr catalytic cycle. First, we describe the crystal structure of Ohr from Xylella fastidiosa (XfOhr) in the open state that, together with the previously described XfOhr structure in the closed state, may represent two snapshots along the coordinate of the enzyme-catalyzed reaction. These two structures were used for the experimental validation of molecular dynamics (MD) simulations. MD simulations employing distinct protonation sta...Continue Reading

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Citations

Aug 28, 2020·Frontiers in Cellular and Infection Microbiology·Larissa Valle Guilhen LongoRosana Puccia
Sep 10, 2019·Chemical Reviews·Ari ZeidaRafael Radi

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Methods Mentioned

BETA
X-ray
gel filtration
Circular dichroism

Software Mentioned

Tripos
WHATCHECK
MMFF94
R
PyMOL
SYBYL
Coot
PROCHECK
CCP4i package
SCALA

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