Häse C C, Finkelstein R A
Department of Molecular Microbiology and Immunology, School of Medicine, University of Missouri, Columbia 65212.
Microbiol Rev. 1993 Dec;57(4):823-37. doi: 10.1128/mr.57.4.823-837.1993.
Extracellular zinc-containing metalloproteases are widely distributed in the bacterial world. The most extensively studied are those which are associated with pathogenic bacteria or bacteria which have industrial significance. They are found practically wherever they are sought in both gram-negative and gram-positive microorganisms, be they aerobic or anaerobic. This ubiquity in itself implies that these enzymes serve important functions for the organisms which produce them. Because of the importance of zinc to enzymatic activity, it is not surprising that there is a pervasive amino acid sequence homology in the primary structure of this family of enzymes regardless of their source. The evidence suggests that both convergent and divergent evolutionary forces are at work. Within the large family of bacterial zinc-containing metalloendopeptidases, smaller family units are observed, such as thermolysin-like, elastase-like, and Serratia protease-like metalloproteases from various bacterial species. While this review was in the process of construction, a new function for zinc-containing metalloproteases was discovered: the neurotoxins of Clostridium tetani and Clostridium botulinum type B have been shown to be zinc metalloproteases with specificity for synaptobrevin, an integral membrane protein of small synaptic vesicles which is involved in neurotransmission. Additional understanding of the mode of action of proteases which contribute to pathogenicity could lead to the development of inhibitors, such as chelators, surrogate substrates, or antibodies, which could prevent or interrupt the disease process. Further studies of this broad family of metalloproteases will provide important additional insights into the pathogenesis and structure-function relationships of enzymes and will lead to the development of products, including "designer proteins," which might be industrially and/or therapeutically useful.
细胞外含锌金属蛋白酶广泛分布于细菌界。研究最为广泛的是那些与病原菌或具有工业意义的细菌相关的酶。在革兰氏阴性菌和革兰氏阳性菌中,无论它们是需氧菌还是厌氧菌,几乎在任何寻找它们的地方都能发现这些酶。这种普遍存在本身就意味着这些酶对产生它们的生物体起着重要作用。由于锌对酶活性的重要性,毫不奇怪,无论其来源如何,这个酶家族的一级结构中都存在普遍的氨基酸序列同源性。有证据表明趋同进化和分歧进化力量都在起作用。在庞大的细菌含锌金属内肽酶家族中,可以观察到较小的家族单位,例如来自各种细菌物种的嗜热菌蛋白酶样、弹性蛋白酶样和粘质沙雷氏菌蛋白酶样金属蛋白酶。在撰写本综述的过程中,发现了含锌金属蛋白酶的一种新功能:破伤风梭菌和肉毒杆菌B型的神经毒素已被证明是对突触小泡蛋白具有特异性的锌金属蛋白酶,突触小泡蛋白是参与神经传递的小突触囊泡的一种整合膜蛋白。对有助于致病性的蛋白酶作用模式的进一步了解可能会导致抑制剂的开发,如螯合剂、替代底物或抗体,它们可以预防或中断疾病进程。对这个广泛的金属蛋白酶家族的进一步研究将为酶的发病机制和结构 - 功能关系提供重要补充见解,并将导致包括“设计蛋白”在内的产品的开发,这些产品可能在工业和/或治疗方面有用。