Crystal Structures of Ligand-Bound Saccharopine Dehydrogenase from Saccharomyces cerevisiae

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• 作者：Babak Andi ; Hengyu Xu ; Paul F. Cook ; Ann H. West
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：November 6, 2007
• 年：2007
• 卷：46
• 期：44
• 页码：12512 - 12521
• 全文大小：770K
• 年卷期：v.46,no.44(November 6, 2007)
• ISSN：1520-4995

文摘

Three structures of saccharopine dehydrogenase (L-lysine-forming) (SDH) have been determinedin the presence of sulfate, adenosine monophosphate (AMP), and oxalylglycine (OxGly). In the sulfate-bound structure, a sulfate ion binds in a cleft between the two domains of SDH, occupies one of thesubstrate carboxylate binding sites, and results in partial closure of the active site of the enzyme due toa domain rotation of almost 12 in comparison to the apoenzyme structure. In the second structure, AMPbinds to the active site in an area where the NAD⁺ cofactor is expected to bind. All of the AMP moieties(adenine ring, ribose, and phosphate) interact with specific residues of the enzyme. In the OxGly-boundstructure, carboxylates of OxGly interact with arginine residues representative of the manner in whichsubstrate (-ketoglutarate and saccharopine) may bind. The -keto group of OxGly interacts with Lys77and His96, which are candidates for acid-base catalysis. Analysis of ligand-enzyme interactions,comparative structural analysis, corroboration with kinetic data, and discussion of a ternary complex modelare presented in this study.