Abramson S R, Conner G E, Nagase H, Neuhaus I, Woessner J F
Department of Biochemistry, University of Miami School of Medicine, Florida 33136, USA.
J Biol Chem. 1995 Jul 7;270(27):16016-22. doi: 10.1074/jbc.270.27.16016.
A small uterine metalloproteinase of the rat has been shown by amino acid and cDNA sequencing to be orthologous to human pump-1. Both proteinases are now designated as matrilysin or matrix metalloproteinase 7. The properties of purified uterine metalloproteinase and recombinant pump-1 were compared. Their specificities on substrates (gelatins, fibronectin, transferrin, elastin, Azocoll, and (7-methoxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-(3,[2, 4-dinitrophenyl]-L-2, 3-diaminopropionyl)-Ala-Arg-NH2) are similar and distinct from those of the stromelysins and gelatinases. The two matrilysins have similar sensitivity to hydroxamate and pseudopeptide inhibitors. Rat matrilysin selectively cleaves the alpha 2(I) chain of rat gelatin, producing major cuts at Gly713-decreases-Ile714, Gly775-decreases-Leu776, and Gly809-decreases-Ile810. Rat matrilysin produces maximum activation of latent human interstitial collagenase 1 (pro-matrix metalloproteinase 1) when added in the presence of 4-aminophenylmercuric acetate (APMA) by cleaving the Gln80-decreases-Phe81 bond. Rat and human matrilysin do not directly activate latent rat collagenase 3 (matrix metalloproteinase 13) and do not enhance its activation when added together with APMA. Autoactivation of collagenase 3 in the presence of APMA results in cleavage at Val81-decreases-Tyr82 corresponding to the Gln80-decreases-Phe81 cleavage in collagenase 1. Thus collagenase 3 is capable of maximal autoactivation, whereas collagenase 1 is dependent upon another matrix metalloproteinase in order to be activated to its full potential.
通过氨基酸和cDNA测序已表明，大鼠的一种小型子宫金属蛋白酶与人泵-1直系同源。这两种蛋白酶现在都被命名为基质溶素或基质金属蛋白酶7。对纯化的子宫金属蛋白酶和重组泵-1的特性进行了比较。它们对底物（明胶、纤连蛋白、转铁蛋白、弹性蛋白、偶氮胶原以及(7-甲氧基香豆素-4-基)乙酰基-Pro-Leu-Gly-Leu-(3,[2,4-二硝基苯基]-L-2,3-二氨基丙酰基)-Ala-Arg-NH2）的特异性相似，且与基质溶解素和明胶酶不同。这两种基质溶素对羟肟酸和假肽抑制剂的敏感性相似。大鼠基质溶素选择性切割大鼠明胶的α2(I)链，主要在Gly713-↓-Ile714、Gly775-↓-Leu776和Gly809-↓-Ile810处产生切割。当在乙酸4-氨基苯汞（APMA）存在下添加大鼠基质溶素时，通过切割Gln80-↓-Phe81键，可使潜在的人间质胶原酶1（前基质金属蛋白酶1）产生最大程度的激活。大鼠和人基质溶素不直接激活潜在的大鼠胶原酶3（基质金属蛋白酶13），并且当与APMA一起添加时也不会增强其激活作用。在APMA存在下胶原酶3的自激活导致在Val81-↓-Tyr82处切割，这与胶原酶1中的Gln80-↓-Phe81切割相对应。因此，胶原酶3能够进行最大程度的自激活，而胶原酶1为了充分激活则依赖于另一种基质金属蛋白酶。
