Yang Z, Floyd D L, Loeber G, Tong L
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Nat Struct Biol. 2000 Mar;7(3):251-7. doi: 10.1038/73378.
Malic enzymes are widely distributed in nature and have many biological functions. The crystal structure of human mitochondrial NAD(P)+-dependent malic enzyme in a quaternary complex with NAD+, Mn++ and oxalate has been determined at 2.2 A resolution. The structures of the quaternary complex with NAD+, Mg++, tartronate or ketomalonate have been determined at 2.6 A resolution. The structures show the enzyme in a closed form in these complexes and reveal the binding modes of the cation and the inhibitors. The divalent cation is coordinated in an octahedral fashion by six ligating oxygens, two from the substrate/inhibitor, three from Glu 255, Asp 256 and Asp 279 of the enzyme, and one from a water molecule. The structural information has significant implications for the catalytic mechanism of malic enzymes and identifies Tyr 112 and Lys 183 as possible catalytic residues. Changes in tetramer organization of the enzyme are also observed in these complexes, which might be relevant for its cooperative behavior and allosteric control.
苹果酸酶在自然界中广泛分布，具有多种生物学功能。已在2.2埃分辨率下确定了人线粒体NAD(P)+依赖性苹果酸酶与NAD+、Mn++和草酸盐形成的四聚体复合物的晶体结构。已在2.6埃分辨率下确定了与NAD+、Mg++、酒石酸或酮丙二酸形成的四聚体复合物的结构。这些结构显示酶在这些复合物中呈封闭形式，并揭示了阳离子和抑制剂的结合模式。二价阳离子通过六个配位氧以八面体方式配位，其中两个来自底物/抑制剂，三个来自酶的Glu 255、Asp 256和Asp 279，一个来自水分子。该结构信息对苹果酸酶的催化机制具有重要意义，并确定Tyr 112和Lys 183为可能的催化残基。在这些复合物中还观察到酶的四聚体组织变化，这可能与其协同行为和变构控制有关。
