Crystal Structure of the Malic Enzyme from Ascaris suum Complexed with Nicotinamide Adenine Dinucleotide at 2.3 Å Resolution

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• 作者：David E. Coleman ; G. S. Jagannatha Rao ; E. J. Goldsmith ; Paul F. Cook ; and Ben G. Harris
• 刊名：Biochemistry
• 出版年：2002
• 出版时间：June 4, 2002
• 年：2002
• 卷：41
• 期：22
• 页码：6928 - 6938
• 全文大小：899K
• 年卷期：v.41,no.22(June 4, 2002)
• ISSN：1520-4995

文摘

The structure of the Ascaris suum mitochondrial NAD-malic enzyme in binary complex withNAD has been solved to a resolution of 2.3 Å by X-ray crystallography. The structure resembles that ofthe human mitochondrial enzyme determined in complex with NAD [Xu, Y., Bhargava, G., Wu, H.,Loeber, G., and Tong, L. (1999) Structure 7, 877-889]. The enzyme is a tetramer comprised of subunitspossessing four domains organized in an "open" structure typical of the NAD-bound form. The subunitorganization, as in the human enzyme, is a dimer of dimers. The Ascaris enzyme contains 30 additionalresidues at its amino terminus relative to the human enzyme. These residues significantly increase theinteractions that promote tetramer formation and give rise to different subunit-subunit interactions. Unlikethe mammalian enzyme, the Ascaris malic enzyme is not regulated by ATP, and no ATP binding site isobserved in this structure. Although the active sites of the two enzymes are similar, residues interactingwith NAD differ between the two. The structure is discussed in terms of the mechanism and particularlywith respect to previously obtained kinetic and site-directed mutagenesis experiments.