Winyard P G, Zhang Z, Chidwick K, Blake D R, Carrell R W, Murphy G
Inflammation Research Group, London Hospital Medical College, UK.
FEBS Lett. 1991 Feb 11;279(1):91-4. doi: 10.1016/0014-5793(91)80258-5.
alpha 1 Antitrypsin (alpha 1AT) is the main physiological inhibitor of neutrophil elastase, a serine protease which has been implicated in tissue degradation at inflammatory sites. We report here that the connective tissue metalloproteinase, stromelysin, cleaved alpha 1AT (54 kDa), producing fragments of approximately 50 kDa and 4 kDa, as shown by gel electrophoresis. The cleavage of alpha 1AT was accompanied by inactivation of its elastase inhibitory capacity. Isolation of the 4 kDa fragment by reversed-phase HPLC, followed by N-terminal amino acid sequencing, demonstrated that the cleavage of alpha 1AT occurred at the Pro357-Met358 (P2-P1) peptide bond, one peptide bond to the N-terminal side of the inhibitory site. We suggest that stromelysin may potentiate the activity of neutrophil elastase by proteolytically inactivating alpha 1AT.
α1抗胰蛋白酶（α1AT）是中性粒细胞弹性蛋白酶的主要生理抑制剂，中性粒细胞弹性蛋白酶是一种丝氨酸蛋白酶，与炎症部位的组织降解有关。我们在此报告，结缔组织金属蛋白酶基质溶解素可切割α1AT（54 kDa），产生约50 kDa和4 kDa的片段，如凝胶电泳所示。α1AT的切割伴随着其弹性蛋白酶抑制能力的失活。通过反相高效液相色谱法分离4 kDa片段，随后进行N端氨基酸测序，结果表明α1AT的切割发生在Pro357-Met358（P2-P1）肽键处，该肽键位于抑制位点N端一侧的一个肽键处。我们认为，基质溶解素可能通过蛋白水解使α1AT失活来增强中性粒细胞弹性蛋白酶的活性。
