Electronic Control of Ligand-Binding Preference of a Myoglobin Mutant

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• 作者：Ryu Nishimura ; Daichi Matsumoto ; Tomokazu Shibata ; Sachiko Yanagisawa ; Takashi Ogura ; Hulin Tai ; Takashi Matsuo ; Shun Hirota ; Saburo Neya ; Akihiro Suzuki ; Yasuhiko Yamamoto
• 刊名：Inorganic Chemistry
• 出版年：2014
• 出版时间：September 2, 2014
• 年：2014
• 卷：53
• 期：17
• 页码：9156-9165
• 全文大小：473K
• ISSN：1520-510X

文摘

The L29F mutant of sperm whale myoglobin (Mb), where the leucine 29 residue was replaced by phenylalanine (Phe), was shown to exhibit remarkably high affinity to oxygen (O₂), possibly due to stabilization of the heme Fe atom-bound O₂ in the mutant protein through a proposed unique electrostatic interaction with the introduced Phe29, in addition to well-known hydrogen bonding with His64 [Carver, T. E.; Brantley, R. E.; Singleton, E. W.; Arduini, R. M.; Quillin, M. L.; Phillips, G. N., Jr.; Olson, J. S. J. Biol. Chem., 1992, 267, 14443鈥?4450]. We analyzed the O₂ and carbon monoxide (CO) binding properties of the L29F mutant protein reconstituted with chemically modified heme cofactors possessing a heme Fe atom with various electron densities, to determine the effect of a change in the electron density of the heme Fe atom (蟻_Fe) on the O₂ versus CO discrimination. The study demonstrated that the preferential binding of O₂ over CO by the protein was achieved through increasing 蟻_Fe, and the ordinary ligand-binding preference, that is, the preferential binding of CO over O₂, by the protein was achieved through decreasing 蟻_Fe. Thus, the O₂ and CO binding preferences of the L29F mutant protein could be controlled through electronic modulation of intrinsic heme Fe reactivity through a change in 蟻_Fe. The present study highlighted the significance of the tuning of the intrinsic heme Fe reactivity through the heme electronic structure in functional regulation of Mb.