晶体结构的以前双核的锌beta-lactamase脆弱拟杆菌。
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没有外耳,拉斯穆森英航,布什K,赫兹伯格O
晶体结构的以前双核的锌beta-lactamase脆弱拟杆菌。
结构。1996年7月15日,4 (7):823 - 36。
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8805566 (在PubMed]
- 文摘
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背景:脆弱拟杆菌的金属-β-内酰胺酶水解各种beta-lactam抗生素,而不是临床容易受到任何已知beta-lactamase抑制剂。b . fragilis与对象有关医院感染,有最近的一份报告plasmid-mediated传播的酶。因此有效的抑制剂是急需的。三维结构的知识将有助于药物设计工作。结果:酶的晶体结构决定了使用多波长反常衍射锌吸收边缘分辨率1.85和精制。结构是一个基础课α/βα/β/分子。活动网站,发现β三明治的边缘包含双核的锌中心一些新颖的特点。锌是四面体地协调,其他三方双锥体协调;水/氢氧分子作为配体的金属。协调两个锌是不变的残留所有金属-β-内酰胺酶测序,除了两个保守的替代品。 Despite the existence of the pattern for binuclear zinc binding, the reported structure of the Bacillus cereus enzyme contains only a single zinc. CONCLUSIONS: Structural analysis indicates that affinity for the penta-coordinated zinc can be modulated by neighboring residues, perhaps explaining the absence of the second zinc in the B. cereus structure. Models of bound substrates suggest that the active-site channel can accommodate a wide variety of beta-lactams. We propose that the zinc cluster prepares an hydroxide, probably the hydroxide that ligates both zincs, for nucleophilic attack on the carbonyl carbon atom of the beta-lactam. The resulting negatively charged tetrahedral intermediate implicated in catalysis is stabilized by an oxyanion hole formed by the side chain of the invariant Asn 193 and the tetrahedral zinc.