Woods Virgil A, Sharma Shivani, Lemberikman Alexis M, Keedy Daniel A
Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY 10031, USA; PhD Program in Biochemistry, CUNY Graduate Center, New York, NY 10016, USA.
Structural Biology Initiative, CUNY Advanced Science Research Center, New York, NY 10031, USA; PhD Program in Biology, CUNY Graduate Center, New York, NY 10016, USA.
Curr Opin Struct Biol. 2025 Aug 1;94:103125. doi: 10.1016/j.sbi.2025.103125.
Protein tyrosine phosphatases (PTPs) are a family of enzymes that play critical roles in intracellular signaling and regulation. PTPs are conformationally dynamic, exhibiting motions of catalytic loops and additional regions of the structurally conserved catalytic domain. However, many questions remain about how dynamics contribute to catalysis and allostery in PTPs, how these behaviors vary among evolutionarily divergent PTP family members, and how mutations and ligands reshape dynamics to modulate PTP function. Recently, our understanding in these areas has expanded significantly, thanks to novel applications of existing methods and emergence of new approaches in structural biology and biophysics. Here we review exciting advances in this realm from the last few years. We organize our commentary both by experimental and computational methodologies, including solution techniques, avant-garde crystallography, molecular dynamics simulations, and bioinformatics, and also by scientific focus, including regulatory mechanisms, mutations and protein engineering, and small-molecule ligands such as allosteric modulators.
蛋白质酪氨酸磷酸酶（PTPs）是一类在细胞内信号传导和调节中起关键作用的酶。PTPs具有构象动力学特性，其催化环和结构保守催化结构域的其他区域会发生运动。然而，关于动力学如何促进PTPs的催化和变构、这些行为在进化上不同的PTP家族成员之间如何变化，以及突变和配体如何重塑动力学以调节PTP功能，仍存在许多问题。最近，由于现有方法的新应用以及结构生物学和生物物理学中新方法的出现，我们在这些领域的理解有了显著扩展。在此，我们回顾过去几年在这一领域取得的令人兴奋的进展。我们通过实验和计算方法（包括溶液技术、前沿晶体学、分子动力学模拟和生物信息学）以及科学重点（包括调节机制、突变和蛋白质工程以及变构调节剂等小分子配体）来组织我们的评论。
