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Protein Engineering vol. 16 no. 6 pp. 435-441, 2003
© 2003 Oxford University Press

Role of tryptophan 121 in the soluble CuA domain of cytochrome c oxidase: structure and electron transfer studies

Ai-Xin Song1, Lian-Zhi Li1, Ting Yu1, Shi-Ming Chen2 and Zhong-Xian Huang1,3

1Chemical Biology Laboratory, Department of Chemistry and 2Research Center for Analysis and Measurement, Fudan University, Shanghai 200433, China

3 To whom correspondence should be addressed. e-mail: zxhuang{at}fudan.edu.cn

To investigate the contribution of tryptophan-121 (Trp121) residue to the structure and function of soluble CuA domain of cytochrome c oxidase, three mutant proteins, Trp121Tyr, Trp121Leu and Trp121-deleted mutant of the soluble domain of Paracoccus versutus cytochrome c oxidase, were constructed and expressed in Escherichia coli BL21 (DE3). Optical spectral studies showed that both the coordination structure of the CuA center and the secondary structure of the protein were changed significantly in the Leu substitution and deletion mutants of Trp121. Their electron transfer activity with cytochrome c was inhibited severely, as shown in stopped-flow kinetic studies. However, the CuA center can be reconstructed in the Trp121Tyr mutant although its stability decreases compared with the wild-type protein. This mutant keeps the same secondary structure as the wild-type protein, but can only transfer electrons with cytochrome c at a rate of one-seventh-fold. Based on the information on the structure, we also investigated and analyzed the possible factors that affect electron transfer. It appears that the aromatic ring, the size of the side chain and the hydrogen bonding ability of the Trp121 are crucial to the structure and function of the soluble CuA domain.

Received September 11, 2002; revised February 26, 2003; accepted May 27, 2003.


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