We have reported the de novo design of a 4 helix bundle protein with built in conformational gating that couples helical rotation to histidine ligation of heme (Huang, S. S., Koder, R. L., Lewis, M., Wand, A. J., Dutton, P. L. PNAS 101(15) pp 5536-41 2004). Here we exploit the molecular strain of this rotation to control tight, reversible binding of O2 to heme without rapid electron transfer, functions performed in nature by the transport and storage proteins hemoglobin and myoglobin. Surprisingly, this designed protein displays much better discrimination against the physiological toxin CO than native O2 carriers. While hemoglobin suppresses the 10,000 fold greater affinity of free heme for CO over O2 to a tolerable 100 fold greater affinity, the designed helical bundle protein rejects CO in favor of O2 by over an order of magnitude.
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