A demetallation method for IMP-1 metallo-ss-lactamase with restored enzymatic activity upon addition of metal ion(s)
A demetallation method for IMP-1 metallo-ss-lactamase with restored enzymatic activity upon addition of metal ion(s)
复制标题
IMP-1 金属-β-内酰胺酶的脱金属方法，添加金属离子后酶活性恢复
DOI：
10.1002/cbic.201100342
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发表时间：
2011
期刊：
影响因子：
3.2
通讯作者：
Kurosaki H
中科院分区：
文献类型：
--
作者：
Yamaguchi Y;Ding S;Murakami E;Imamura K;Fuchigami S;Hashiguchi R;Yutani K;Mori H;Suzuki S;Arakawa Y;Kurosaki H
金属β-内酰胺酶(Mbls)是一种依赖锌的酶，能降解大多数β-内酰胺类[1]，由于其广泛的底物专一性和缺乏临床上可用的抑制剂而在临床环境中构成潜在的威胁。[2]根据活性中心的一组金属离子配体，MBLS被分为三个亚类，B1，B2和B3。[3]最近，印度、巴基斯坦以及英国[4]和许多其他国家发现了一种新的金属β-内酰胺酶。金属β-内酰胺酶的进一步增殖正成为一个严重的全球公共卫生问题。[5]在目前已知的MBLs中，IMP-1属于B1亚类，是最严重的威胁之一，因为编码它的基因位于一个可在细菌菌株之间水平转移的整合子结构中。测定了IMP-1的X-射线晶体结构，在活性中心发现了两个锌离子(称为锌离子)，其中锌离子与His116、His118和His196配位，而锌离子与Asp120、Cys221、His263和水分子配位(图1)。此外，尽管由于晶体结构的低分辨率，没有观察到这种分子的电子密度，但人们认为OH2或OH±是桥接在锌1和锌2之间的。
Metallo-β-lactamases (MBLs) are ZnII-dependent enzymes that hydrolyze most β-lactams [1] and pose a potential threat in clinical environments due to their wide substrate specificity and lack of clinically available inhibitors.[2] MBLs are classified into three subclasses, B1, B2, and B3, according to the set of metal ion ligands in the active center.[3] Most recently, a new metalloβ-lactamase has been found in India, Pakistan, and also in the United Kingdom [4] and many other countries. Further proliferation of the types of metallo-β-lactamases is becoming a grave worldwide public health concern.[5] Among the currently known MBLs, IMP-1, belonging to subclass B1, is one of the most serious threats because the gene encoding it is located in an integron structure on a plasmid,[6] which is horizontally transferable between bacterial strains. The X-ray crystal structure of IMP-1 has been determined and two ZnII ions (termed Zn1 and Zn2) were found in the active center.[7] Zn1 is tetrahedrally coordinated by His116, His118, and His196, whereas Zn2 is trigonal–pyramidally coordinated by Asp120, Cys221, His263, and a water molecule (Figure 1). In addition, OH2 or OHÀ is thought to be bridged between Zn1 and Zn2, although no electron density for this molecule is observed due to the low resolution of the crystal structure.