Stuckey J A, Dixon J E
Department of Biological Chemistry, The University of Michigan, Ann Arbor 48109-0606, USA.
Nat Struct Biol. 1999 Mar;6(3):278-84. doi: 10.1038/6716.
The first crystal structure of a phospholipase D (PLD) family member has been determined at 2.0 A resolution. The PLD superfamily is defined by a common sequence motif, HxK(x)4D(x)6GSxN, and includes enzymes involved in signal transduction, lipid biosynthesis, endonucleases and open reading frames in pathogenic viruses and bacteria. The crystal structure suggests that residues from two sequence motifs form a single active site. A histidine residue from one motif acts as a nucleophile in the catalytic mechanism, forming a phosphoenzyme intermediate, whereas a histidine residue from the other motif appears to function as a general acid in the cleavage of the phosphodiester bond. The structure suggests that the conserved lysine residues are involved in phosphate binding. Large-scale genomic sequencing revealed that there are many PLD family members. Our results suggest that all of these proteins may possess a common structure and catalytic mechanism.
已确定磷脂酶D（PLD）家族成员的首个晶体结构，分辨率为2.0埃。PLD超家族由一个共同的序列基序HxK(x)4D(x)6GSxN界定，包括参与信号转导、脂质生物合成、核酸内切酶以及致病病毒和细菌中的开放阅读框的酶。晶体结构表明，来自两个序列基序的残基形成一个单一的活性位点。一个基序中的组氨酸残基在催化机制中作为亲核试剂，形成磷酸酶中间体，而另一个基序中的组氨酸残基似乎在磷酸二酯键的裂解中作为广义酸发挥作用。该结构表明，保守的赖氨酸残基参与磷酸盐结合。大规模基因组测序显示有许多PLD家族成员。我们的结果表明，所有这些蛋白质可能具有共同的结构和催化机制。
