School of Life Science and Biotechnology, Dalian University of Technology, Dalian, China.
Curr Drug Targets. 2012 Apr;13(4):512-25. doi: 10.2174/138945012799499730.
Glycosyl hydrolase family 3, 20 and 84 β-N-acetyl-D-hexosaminidases are widely distributed enzymes that function in energy metabolism, cell proliferation, signal transduction as well as in pathogen-related inflammation and autoimmune diseases. Sharing the same retaining catalytic mechanism, they are distinguished from each other in terms of structure rather than substrate-enzyme transition state. Selective inhibition of each of these enzymes that exploits the structural differences would appear promising in the regulation and investigation of their corresponding life functions within the organism. Thanks to molecular structural biology, detailed structures of GH3, 20 and 84 β-N-acetyl-Dhexosaminidases have become available at the atomic level. This review gives a panoramic description and comparison of the enzymes catalytic mechanisms, overall structures, active site architectures as well as structure-based analysis of inhibition, with the hope of exploiting novel targets for developing novel drugs and pesticides.
糖苷水解酶家族 3、20 和 84β-N-乙酰-D-氨基葡萄糖苷酶是广泛分布的酶，它们在能量代谢、细胞增殖、信号转导以及与病原体相关的炎症和自身免疫疾病中发挥作用。这些酶具有相同的保留催化机制，但在结构上彼此不同，而不是在底物-酶过渡态上不同。选择性抑制这些酶中的每一种，利用结构差异，在调节和研究它们在生物体中的相应生命功能方面似乎很有前景。由于分子结构生物学的发展，GH3、20 和 84β-N-乙酰-D-氨基葡萄糖苷酶的详细结构已在原子水平上获得。本文全面描述和比较了这些酶的催化机制、整体结构、活性位点结构以及基于结构的抑制分析，以期开发新型药物和农药，寻找新的靶标。
