Freigang Jörg, Diederichs Kay, Schäfer Klaus P, Welte Wolfram, Paul Ralf
Fachbereich Biologie, Universität Konstanz, D-78457 Konstanz, Germany.
Protein Sci. 2002 Feb;11(2):253-61. doi: 10.1110/ps.28602.
The redox protein flavodoxin has been shown earlier to be reduced by the pyruvate-oxidoreductase (POR) enzyme complex of Helicobacter pylori, and also was proposed to be involved in the pathogenesis of gastric mucosa-associated lymphoid-tissue lymphoma (MALToma). Here, we report its X-ray structure, which is similar to flavodoxins of other bacteria and cyanobacteria. However, H. pylori flavodoxin has an alanine residue near the isoalloxazine ring of its cofactor flavin mononucleotide (FMN), while the other previously crystallized flavodoxins have a larger hydrophobic residue at this position. This creates a solute filled hole near the FMN cofactor of H. pylori flavodoxin. We also show that flavodoxin is essential for the survival of H. pylori, and conclude that its structure can be used as a starting point for the modeling of an inhibitor for the interaction between the POR-enzyme complex and flavodoxin.
氧化还原蛋白黄素氧还蛋白此前已被证明可被幽门螺杆菌的丙酮酸氧化还原酶（POR）酶复合物还原，并且还被认为与胃黏膜相关淋巴组织淋巴瘤（MALToma）的发病机制有关。在此，我们报告了其X射线结构，该结构与其他细菌和蓝细菌的黄素氧还蛋白相似。然而，幽门螺杆菌黄素氧还蛋白在其辅因子黄素单核苷酸（FMN）的异咯嗪环附近有一个丙氨酸残基，而其他先前结晶的黄素氧还蛋白在该位置有一个更大的疏水残基。这在幽门螺杆菌黄素氧还蛋白的FMN辅因子附近形成了一个溶质填充孔。我们还表明黄素氧还蛋白对幽门螺杆菌的存活至关重要，并得出结论，其结构可作为模拟POR酶复合物与黄素氧还蛋白之间相互作用抑制剂的起点。
