Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog
Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog
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DOI：
10.1038/nsb882
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发表时间：
2003-01-01
期刊：
影响因子：
--
通讯作者：
Wagtmann, N
中科院分区：
文献类型：
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作者：
Rasmussen, HB;Branner, S;Wagtmann, N
二肽基肽酶IV（DPP-IV/CD 26）是一种多功能的II型跨膜丝氨酸肽酶。这种酶通过切割肽激素、趋化因子和神经肽，有助于调节各种生理过程，包括血糖稳态。我们已经确定了与抑制剂缬氨酸-吡咯烷复合的DPP-IV胞外区的2.5埃结构。催化位点位于α/β-水解酶结构域和八叶β-螺旋桨结构域之间形成的大空腔中。两个结构域都参与抑制剂结合。结构表明如何实现底物特异性，并揭示了一个新的和意想不到的开放的活性位点。
Dipeptidyl peptidase IV (DPP-IV/CD26) is a multifunctional type II transmembrane serine peptidase. This enzyme contributes to the regulation of various physiological processes, including blood sugar homeostasis, by cleaving peptide hormones, chemokines and neuropeptides. We have determined the 2.5 Angstrom structure of the extracellular region of DPP-IV in complex with the inhibitor valine-pyrrolidide. The catalytic site is located in a large cavity formed between the alpha/beta-hydrolase domain and an eight-bladed beta-propeller domain. Both domains participate in inhibitor binding. The structure indicates how substrate specificity is achieved and reveals a new and unexpected opening to the active site.