Barford D, Das A K, Egloff M P
Laboratory of Molecular Biophysics, University of Oxford, United Kingdom.
Annu Rev Biophys Biomol Struct. 1998;27:133-64. doi: 10.1146/annurev.biophys.27.1.133.
Eukaryotic protein phosphatases are structurally and functionally diverse enzymes that are represented by three distinct gene families. Two of these, the PPP and PPM families, dephosphorylate phosphoserine and phosphothreonine residues, whereas the protein tyrosine phosphatases (PTPs) dephosphorylate phosphotyrosine amino acids. A subfamily of the PTPs, the dual-specificity phosphatases, dephosphorylate all three phosphoamino acids. Within each family, the catalytic domains are highly conserved, with functional diversity endowed by regulatory domains and subunits. The protein Ser/Thr phosphatases are metalloenzymes and dephosphorylate their substrates in a single reaction step using a metal-activated nucleophilic water molecule. In contrast, the PTPs catalyze dephosphorylation by use of a cysteinyl-phosphate enzyme intermediate. The crystal structures of a number of protein phosphatases have been determined, enabling us to understand their catalytic mechanisms and the basis for substrate recognition and to begin to provide insights into molecular mechanisms of protein phosphatase regulation.
真核生物蛋白磷酸酶是结构和功能多样的酶，由三个不同的基因家族代表。其中两个家族，即PPP和PPM家族，使磷酸丝氨酸和磷酸苏氨酸残基去磷酸化，而蛋白酪氨酸磷酸酶（PTP）则使磷酸酪氨酸氨基酸去磷酸化。PTP的一个亚家族，即双特异性磷酸酶，能使所有三种磷酸氨基酸去磷酸化。在每个家族中，催化结构域高度保守，其功能多样性由调节结构域和亚基赋予。蛋白丝氨酸/苏氨酸磷酸酶是金属酶，在单个反应步骤中使用金属激活的亲核水分子使其底物去磷酸化。相比之下，PTP通过使用半胱氨酰 - 磷酸酶中间体催化去磷酸化。已经确定了许多蛋白磷酸酶的晶体结构，这使我们能够了解它们的催化机制以及底物识别的基础，并开始深入了解蛋白磷酸酶调节的分子机制。
