Avilés F X, Vendrell J, Guasch A, Coll M, Huber R
Departament de Bioquímica (Fac. Ciències), Universitat Autònoma de Barcelona, Spain.
Eur J Biochem. 1993 Feb 1;211(3):381-9. doi: 10.1111/j.1432-1033.1993.tb17561.x.
Our knowledge on the structure and functionality of pancreatic carboxypeptidases is rapidly expanding to include that of their zymogen forms. The recent application of fast and mild isolation procedures, together with modern molecular genetic and biochemical-biophysical characterization approaches, has provided a clearer view of the basic structures and functional states in which these zymogens occur, and their evolutionary relationships. The same holds for related metallo-carboxypeptidases, either in the pro or active forms, that have been isolated and characterized in non-digestive fluids and tissues, where they probably play an important role in protein and peptide processing. The determination of the three-dimensional structure of the A and B pancreatic zymogens has revealed the molecular determinants of their inactivity and proteolytic activation. The folding of their 95-residue activation segment in a globular N-terminal domain (74-81 residues) and in a connecting region (20-14 residues), and the specific contacts of these pieces with the substrate binding sites of the enzyme, are important factors in zymogen inhibition. On the other hand, the different length of the alpha-helical connecting region and the stability of its contacts with the enzyme account for the different activation properties of A and B zymogens.
我们对胰腺羧肽酶结构和功能的认识正在迅速扩展，涵盖其酶原形式。快速温和的分离程序与现代分子遗传学及生物化学-生物物理表征方法的近期应用，使我们对这些酶原存在的基本结构和功能状态及其进化关系有了更清晰的认识。在非消化液和组织中分离并表征的相关金属羧肽酶，无论是前体形式还是活性形式，情况也是如此，它们可能在蛋白质和肽的加工过程中发挥重要作用。胰腺A和B酶原三维结构的确定揭示了其无活性和蛋白水解激活的分子决定因素。其95个残基的激活片段在球状N端结构域（74 - 81个残基）和连接区域（20 - 14个残基）中的折叠，以及这些片段与酶的底物结合位点的特定接触，是酶原抑制的重要因素。另一方面，α-螺旋连接区域的不同长度及其与酶接触的稳定性，解释了A和B酶原不同的激活特性。
