Manning M C
Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
Toxicon. 1995 Sep;33(9):1189-200. doi: 10.1016/0041-0101(95)00052-n.
Fibrolase is a small (203 amino acids), nonhemorrhagic, fibrinolytic enzyme from the venom of Agkistrodon contortrix contortrix (southern copperhead). While the chemical and physical properties of the protein have been extensively studied, its overall globular structure is unknown. By comparison with homologous metalloproteinases and snake toxins, the catalytic zinc binding site of fibrolase has been identified, as well as a potential binding site for calcium, which has not been recognized before. The positions of the major secondary structural features are predicted, and found to be similar to other structurally characterized metalloproteinases, while the positions of the three intramolecular disulfide bonds are also postulated. Finally, fibrolase is reported to be nonhemorrhagic and earlier work on hemorrhagic enzymes from snake venoms identified six amino acids which might be responsible for hemorrhagic activity. It is shown here that most of these residues occur in fibrolase, and yet it is nonhemorrhagic in its activity. Altogether, this work demonstrates the utility of sequence analysis methods in the characterization of the structure of venom-derived proteins.
纤维蛋白溶解酶是一种来自南方铜头蝮蛇（Agkistrodon contortrix contortrix）毒液的小型（含203个氨基酸）、无出血毒性的纤维蛋白溶解酶。虽然对该蛋白质的化学和物理性质已进行了广泛研究，但其整体球状结构尚不清楚。通过与同源金属蛋白酶和蛇毒素进行比较，已确定了纤维蛋白溶解酶的催化锌结合位点，以及一个此前未被识别的潜在钙结合位点。预测了主要二级结构特征的位置，发现其与其他已确定结构的金属蛋白酶相似，同时还推测了三个分子内二硫键的位置。最后，据报道纤维蛋白溶解酶无出血毒性，而此前对蛇毒出血酶的研究确定了六个可能与出血活性有关的氨基酸。本文表明，这些残基大多存在于纤维蛋白溶解酶中，但其活性却无出血毒性。总之，这项工作证明了序列分析方法在表征毒液衍生蛋白质结构方面的实用性。
