Supramolecular assembly and acid resistance of Helicobacter pylori urease
Supramolecular assembly and acid resistance of Helicobacter pylori urease
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DOI：
10.1038/88563
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发表时间：
2001-06-01
期刊：
影响因子：
--
通讯作者：
Oh, BH
中科院分区：
文献类型：
--
作者：
Ha, NC;Oh, ST;Oh, BH
幽门螺杆菌是多种胃十二指肠疾病的病原体，它产生大量的脲酶，人们认为脲酶可以通过产生氨来中和胃酸，从而维持细菌的生存。在裂解邻近细菌时，高达 30% 的酶与完整细胞的表面结合。该酶在细胞外位置的作用一直是一个有争议的话题，因为纯化的酶在 pH 值低于 5 的情况下会不可逆地失活。我们已经确定了幽门螺杆菌脲酶的晶体结构，它具有 1.1 MDa 的球形组件，由 12 个催化单元组成，外径约为 160 埃。在生理相关条件下，酶的活性在低至 pH 3 的情况下仍不受影响。不同条件下的活性测定表明，超分子组装体上 12 个活性位点的分散可能对于酶在低 pH 下的存活至关重要。该结构提供了一个适合耐酸性的分子组装的新例子，与酶的低 K-m 值一起，很可能使生物体能够栖息在敌对的生态位中。
Helicobacter pylori, an etiologic agent in a variety of gastroduodenal diseases, produces a large amount of urease, which is believed to neutralize gastric acid by producing ammonia for the survival of the bacteria. Up to 30% of the enzyme associates with the surface of intact cells upon lysis of neighboring bacteria. The role of the enzyme at the extracellular location has been a subject of controversy because the purified enzyme is irreversibly inactivated below pH 5. We have determined the crystal structure of H. pylori urease, which has a 1.1 MDa spherical assembly of 12 catalytic units with an outer diameter of similar to 160 Angstrom. Under physiologically relevant conditions, the activity of the enzyme remains unaffected down to pH 3. Activity assays under different conditions indicated that the duster of the 12 active sites on the supramolecular assembly may be critical for the survival of the enzyme at low pH. The structure provides a novel example of a molecular assembly adapted for acid resistance that, together with the low K-m value of the enzyme, is likely to enable the organism to inhabit the hostile niche.