Dehaloperoxidase (DHP) is a multifunctional hemeprotein with a functional switch generally regulated by the chemical class of the substrate. Its two isoforms, DHP A and DHP B, differ by five amino acids and have an almost identical protein fold. However, the catalytic efficiency of DHP B for oxidation by a peroxidase mechanism is about 3-6 fold greater than DHP A at pH 7, depending on substrate. X-ray crystal structures have shown that a number of substrates have nearly identical internal substrate binding in the two isoenzymes, suggesting that the difference in catalytic efficiency could be due to differences in conformational dynamics. The backbone dynamics of DHP A have been measured by NMR, but there are no previous studies on DHP B. We compared backbone conformational dynamics between the DHP isoenzymes through the measurement of NMR heteronuclear relaxation dynamics and molecular dynamics simulations. Results show that the backbone of DHP B is slightly more flexible (△S2 ~ 0.02) and some key amino acids located at both the distal and proximal cavities are significantly more flexible (△S2 > 0.2). This suggests that the increase in flexibility in DHP B may be correlated with its greater catalytic efficiency.

Differences in heteronuclear relaxation dynamics of dehaloperoxidase-hemoglobin isoenzymes A and B

ACS Fall 2021

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