Fields G B
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
J Theor Biol. 1991 Dec 21;153(4):585-602. doi: 10.1016/s0022-5193(05)80157-2.
Mammalian collagenases cleave all three alpha chains of native, triple-helical types I, II, and III collagens after the Gly residue of the partial sequence Gly-[Ile or Leu]-[Ala or Leu] at a single locus approximately three-fourths from the amino terminus. There are an additional 31 sites in the triple-helical regions of types I, II, III, and IV collagens that contain the same partial sequence but are not hydrolyzed. A model has been developed to explain this remarkable specificity. The mammalian collagenase cleavage site in interstitial collagens is distinguished by: (a) a low side-chain molal volume-, high imino acid (greater than 33%)-containing region that is tightly triple-helical, consisting of four Gly-X-Y triplets preceding the cleavage site, (b) a low imino acid-containing (less than 17%), loosely triple-helical region consisting of four Gly-X-Y triplets following the cleavage site, and (c) a maximum of one charged residue for the entire 25 residue cleavage site region, which is always an Arg that follows the cleavage site in subsite P'5 or P'8. In addition, the high imino acid-containing region cannot have an imino acid adjacent to the cleaved Gly-[Ile or Leu] bond (i.e. in subsite P2). Careful scrutiny of the 31 non-cleaved sequences reveals that none of those sites shares all of the characteristics of the cleavage site. The criterion of this model thus explain both cleaved and non-cleaved sequences in the triple-helical regions of types I, II, III, and IV collagen, and are supported by all known experimental and theoretical results on collagen catabolism and structure.
哺乳动物胶原酶在天然三螺旋结构的I型、II型和III型胶原蛋白的所有三条α链上，于部分序列Gly-[Ile或Leu]-[Ala或Leu]的Gly残基之后、距氨基末端约四分之三的单个位点进行切割。在I型、II型、III型和IV型胶原蛋白的三螺旋区域中，还有31个位点含有相同的部分序列，但未被水解。已建立一个模型来解释这种显著的特异性。间质胶原中哺乳动物胶原酶的切割位点具有以下特征：(a) 一个低侧链摩尔体积、高亚氨基酸（大于33%）的区域，该区域紧密呈三螺旋结构，由切割位点前的四个Gly-X-Y三联体组成；(b) 一个低亚氨基酸含量（小于17%）、松散呈三螺旋结构的区域，由切割位点后的四个Gly-X-Y三联体组成；(c) 在整个25个残基的切割位点区域中最多有一个带电荷残基，该残基总是一个Arg，位于亚位点P'5或P'8中切割位点之后。此外，高亚氨基酸含量区域在被切割的Gly-[Ile或Leu]键（即亚位点P2）相邻位置不能有亚氨基酸。对这31个未切割序列的仔细研究表明，这些位点均不具备切割位点的所有特征。该模型的标准因此解释了I型、II型、III型和IV型胶原蛋白三螺旋区域中的切割和未切割序列，并得到了所有关于胶原分解代谢和结构的已知实验和理论结果的支持。
