A Designed Heme-[4Fe-4S] Metalloenzyme Catalyzes Sulfite Reduction Like the Native Enzyme

CABBI Theme: Conversion

Keyword: Catalysis

Citation

Mirts, E.N., Petrik, I.D., Hosseinzadeh, P., Nilges, M.J., Lu, Y. Sept. 14, 2018. “A Designed Heme-[4Fe-4S] Metalloenzyme Catalyzes Sulfite Reduction Like the Native Enzyme.” Science Vol. 361, Issue 6407, pp. 1098-1101, DOI: 10.1126/science.aat8474.

Iterative testing of different amino acids within the designed binding site yielded increased enzymatic activity.

Overview

Enzymatic reduction of oxyanions such as sulfite (SO₃²⁻) requires the delivery of multiple electrons and protons, a feat accomplished by cofactors tailored for catalysis and electron transport. Replicating this strategy in protein scaffolds may expand the range of enzymes that can be designed de novo. Mirts et al. selected a scaffold protein containing a natural heme cofactor and then engineered a cavity suitable for binding a second cofactor: an iron-sulfur cluster (see the Perspective by Lancaster). The resulting designed enzyme was optimized through rational mutation into a catalyst with spectral characteristics and activity similar to that of natural sulfite reductases.

Data

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Table S1: Parameters for EXAFS best-fit simulations of oxidized and reduced samples of FeS-SiRCc1

Table S2: Reported and measured activities for native sulfite reductase and SiRCcP