A model for the reaction mechanism of the transglutaminase 3 enzyme
A model for the reaction mechanism of the transglutaminase 3 enzyme
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DOI：
10.1038/emm.2003.31
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发表时间：
2003-08-31
影响因子：
12.8
通讯作者：
Steinert, PM
中科院分区：
文献类型：
--
作者：
Ahvazi, B;Steinert, PM
转氨酶（TGases）催化蛋白质结合的谷氨酰胺和赖氨酸底物之间的异肽键的钙依赖性形成。以前我们已经表明，激活的TGase 3在位点2和3获得两个额外的钙离子。第三个位点的钙离子导致通道的开放。在这个部位，通道的打开和关闭可以调节，这取决于结合的金属。在这里，我们提出，前面的通道可以用于酶反应的两个底物。我们建议，谷氨酰胺底物是直接从Trp236到酶，分子对接显示。然后，赖氨酸底物接近开放的活性位点以接合Trp327，导致形成异肽键。此外，TGase 3的结构与其他TGases的直接比较，使我们能够确定几个残基，可能参与通用和特异性识别的谷氨酰胺和赖氨酸底物。
Transglutaminase enzymes (TGases) catalyze the calcium dependent formation of an isopeptide bond between protein-bound glutamine and lysine substrates. Previously we have shown that activated TGase 3 acquires two additional calcium ions at site two and three. The calcium ion at site three results in the opening of a channel. At this site, the channel opening and closing could modulate, depending on which metal is bound. Here we propose that the front of the channel could be used by the two substrates for enzyme reaction. We propose that the glutamine substrate is directed from Trp236 into the enzyme, shown by molecular docking. Then a lysine substrate approaches the opened active site to engage Trp327, leading to formation of the isopeptide bond. Further, direct comparisons of the structures of TGase 3 with other TGases have allowed us to identify several residues that might potentially be involved in generic and specific recognition of the glutamine and lysine substrates.