The structure of Lactococcus lactis thioredoxin reductase reveals molecular features of photo-oxidative damage
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The structure of Lactococcus lactis thioredoxin reductase reveals molecular features of photo-oxidative damage. / Skjoldager, Nicklas; Blanner Bang, Maria; Rykaer, Martin; Björnberg, Olof; Davies, Michael Jonathan; Svensson, Birte; Harris, Pernille; Hägglund, Per.
In: Scientific Reports, Vol. 7, 46282, 04.2017.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - The structure of Lactococcus lactis thioredoxin reductase reveals molecular features of photo-oxidative damage
AU - Skjoldager, Nicklas
AU - Blanner Bang, Maria
AU - Rykaer, Martin
AU - Björnberg, Olof
AU - Davies, Michael Jonathan
AU - Svensson, Birte
AU - Harris, Pernille
AU - Hägglund, Per
PY - 2017/4
Y1 - 2017/4
N2 - The NADPH-dependent homodimeric flavoenzyme thioredoxin reductase (TrxR) provides reducing equivalents to thioredoxin, a key regulator of various cellular redox processes. Crystal structures of photo-inactivated thioredoxin reductase (TrxR) from the Gram-positive bacterium Lactococcus lactis have been determined. These structures reveal novel molecular features that provide further insight into the mechanisms behind the sensitivity of this enzyme toward visible light. We propose that a pocket on the si-face of the isoalloxazine ring accommodates oxygen that reacts with photo-excited FAD generating superoxide and a flavin radical that oxidize the isoalloxazine ring C7α methyl group and a nearby tyrosine residue. This tyrosine and key residues surrounding the oxygen pocket are conserved in enzymes from related bacteria, including pathogens such as Staphylococcus aureus. Photo-sensitivity may thus be a widespread feature among bacterial TrxR with the described characteristics, which affords applications in clinical photo-therapy of drug-resistant bacteria.
AB - The NADPH-dependent homodimeric flavoenzyme thioredoxin reductase (TrxR) provides reducing equivalents to thioredoxin, a key regulator of various cellular redox processes. Crystal structures of photo-inactivated thioredoxin reductase (TrxR) from the Gram-positive bacterium Lactococcus lactis have been determined. These structures reveal novel molecular features that provide further insight into the mechanisms behind the sensitivity of this enzyme toward visible light. We propose that a pocket on the si-face of the isoalloxazine ring accommodates oxygen that reacts with photo-excited FAD generating superoxide and a flavin radical that oxidize the isoalloxazine ring C7α methyl group and a nearby tyrosine residue. This tyrosine and key residues surrounding the oxygen pocket are conserved in enzymes from related bacteria, including pathogens such as Staphylococcus aureus. Photo-sensitivity may thus be a widespread feature among bacterial TrxR with the described characteristics, which affords applications in clinical photo-therapy of drug-resistant bacteria.
KW - Journal Article
U2 - 10.1038/srep46282
DO - 10.1038/srep46282
M3 - Journal article
C2 - 28397795
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 46282
ER -
ID: 182331076