Xu Y, Carr P D, Guss J M, Ollis D L
Research School of Chemistry, Australian National University, Canberra, Australia.
J Mol Biol. 1998 Mar 13;276(5):955-66. doi: 10.1006/jmbi.1997.1582.
Bikunin is a serine protease inhibitor found in the blood serum and urine of humans and other animals. Its sequence shows internal repetition, suggesting that it contains two domains that resemble bovine pancreatic trypsin inhibitor (BPTI). A fragment of bikunin has been crystallised, its structure solved and subsequently refined against 2.5 A data. The two BPTI-like domains pack closely together and are related by an approximate 60 degrees rotation combined with a translation. These domains are very similar to each other and other proteins with this fold. The largest variations occur in the loops responsible for protease recognition. The loops of the first domain are unobstructed by the remaining protein. However, the loops of the second domain are close to the first domain and it is possible that protease binding may be affected or, in some cases, abolished by the presence of the first domain. Thus, cleavage of the two domains could alter the substrate specificity of domain II. Bikunin has a hydrophobic patch close to the N terminus of domain I, which is the most likely site for cell-surface receptor binding. In addition, there is a basic patch at one end of domain II that may be responsible for the inhibition of calcium oxalate crystallization in urine.
bikunin是一种丝氨酸蛋白酶抑制剂，存在于人类和其他动物的血清和尿液中。其序列显示出内部重复，表明它含有两个类似于牛胰蛋白酶抑制剂（BPTI）的结构域。bikunin的一个片段已被结晶，其结构已被解析，并随后根据2.5埃的数据进行了优化。两个类似BPTI的结构域紧密堆积在一起，并通过大约60度的旋转和一个平移相关联。这些结构域彼此非常相似，并且与具有这种折叠的其他蛋白质相似。最大的差异发生在负责蛋白酶识别的环中。第一个结构域的环不受其余蛋白质的阻碍。然而，第二个结构域的环靠近第一个结构域，并且蛋白酶结合可能会受到第一个结构域的存在的影响，或者在某些情况下被消除。因此，两个结构域的切割可能会改变结构域II的底物特异性。bikunin在结构域I的N端附近有一个疏水补丁，这是最有可能与细胞表面受体结合的位点。此外，在结构域II的一端有一个碱性补丁，可能负责抑制尿液中草酸钙的结晶。
