使用生化分析、晶体结构和差示扫描量热法分析对OXA - 163、OXA - 181和OXA - 245进行结构、活性和热稳定性研究。
Structure, activity and thermostability investigations of OXA-163, OXA-181 and OXA-245 using biochemical analysis, crystal structures and differential scanning calorimetry analysis.
作者信息
Lund Bjarte Aarmo, Thomassen Ane Molden, Carlsen Trine Josefine Olsen, Leiros Hanna Kirsti S
机构信息
Department of Chemistry, UiT The Arctic University of Norway, 9037 Tromsø, Norway.
出版信息
Acta Crystallogr F Struct Biol Commun. 2017 Oct 1;73(Pt 10):579-587. doi: 10.1107/S2053230X17013838. Epub 2017 Oct 2.
Abstract
The first crystal structures of the class D β-lactamases OXA-181 and OXA-245 were determined to 2.05 and 2.20 Å resolution, respectively; in addition, the structure of a new crystal form of OXA-163 was resolved to 2.07 Å resolution. All of these enzymes are OXA-48-like and have been isolated from different clinical Klebsiella pneumoniae strains and also from other human pathogens such as Pseudomonas aeruginosa and Escherichia coli. Here, enzyme kinetics and thermostability studies are presented, and the new crystal structures are used to explain the observed variations. OXA-245 had the highest melting point (T = 55.8°C), as determined by differential scanning calorimetry, compared with OXA-163 (T = 49.4°C) and OXA-181 (T = 52.6°C). The differences could be explained by the loss of two salt bridges in OXA-163, and an overall decrease in the polarity of the surface of OXA-181 compared with OXA-245.
摘要
D类β-内酰胺酶OXA-181和OXA-245的首个晶体结构分别解析到2.05 Å和2.20 Å的分辨率；此外，OXA-163一种新晶型的结构解析到2.07 Å的分辨率。所有这些酶都与OXA-48类似，且已从不同的临床肺炎克雷伯菌菌株以及其他人类病原体（如铜绿假单胞菌和大肠杆菌）中分离出来。本文展示了酶动力学和热稳定性研究，并利用新的晶体结构来解释观察到的差异。通过差示扫描量热法测定，与OXA-163（熔点 = 49.4°C）和OXA-181（熔点 = 52.6°C）相比，OXA-245具有最高的熔点（熔点 = 55.8°C）。这些差异可以通过OXA-163中两个盐桥的缺失以及与OXA-245相比OXA-181表面极性的总体降低来解释。
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