神经溶素的结构揭示了一个限制底物进入的深通道。
Structure of neurolysin reveals a deep channel that limits substrate access.
作者信息
Brown C K, Madauss K, Lian W, Beck M R, Tolbert W D, Rodgers D W
机构信息
Department of Molecular and Cellular Biochemistry and Center for Structural Biology, University of Kentucky, Lexington, KY 40536, USA.
出版信息
Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3127-32. doi: 10.1073/pnas.051633198. Epub 2001 Mar 6.
The zinc metallopeptidase neurolysin is shown by x-ray crystallography to have large structural elements erected over the active site region that allow substrate access only through a deep narrow channel. This architecture accounts for specialization of this neuropeptidase to small bioactive peptide substrates without bulky secondary and tertiary structures. In addition, modeling studies indicate that the length of a substrate N-terminal to the site of hydrolysis is restricted to approximately 10 residues by the limited size of the active site cavity. Some structural elements of neurolysin, including a five-stranded beta-sheet and the two active site helices, are conserved with other metallopeptidases. The connecting loop regions of these elements, however, are much extended in neurolysin, and they, together with other open coil elements, line the active site cavity. These potentially flexible elements may account for the ability of the enzyme to cleave a variety of sequences.
通过X射线晶体学研究表明，锌金属肽酶神经溶素在活性位点区域上方有大型结构元件，这些元件使得底物只能通过一条深而窄的通道进入。这种结构解释了这种神经肽酶对没有庞大二级和三级结构的小生物活性肽底物的专一性。此外，建模研究表明，由于活性位点腔的尺寸有限，水解位点N端的底物长度被限制在大约10个残基。神经溶素的一些结构元件，包括一个五链β折叠和两个活性位点螺旋，与其他金属肽酶是保守的。然而，这些元件的连接环区域在神经溶素中大大延长，并且它们与其他开放螺旋元件一起构成了活性位点腔的内壁。这些潜在的柔性元件可能解释了该酶切割多种序列的能力。
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