The three-dimensional structure of VIM-2, a Zn-β-lactamase from Pseudomonas aeruginosa in its reduced and oxidised form
The three-dimensional structure of VIM-2, a Zn-β-lactamase from Pseudomonas aeruginosa in its reduced and oxidised form
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DOI：
10.1016/j.jmb.2007.11.012
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发表时间：
2008-01-18
影响因子：
5.6
通讯作者：
Dideberg, O.
中科院分区：
文献类型：
--
作者：
Garcia-Saez, I.;Docquier, J. -D.;Dideberg, O.
来自铜绿假单胞菌的普遍分布的金属-β-内酰胺酶（MBL）Verona整合子编码的MBL（Vim）-2的晶体结构已经以其天然形式以及以意想不到的氧化形式得到解决。这种碳青霉烯水解酶属于所谓的131 MBL亚家族，并共享α β/β α三明治折叠，由α螺旋包围的β折叠核心组成。令人惊讶的是，它显示出在位于Cys位点的催化半胱氨酸Cys 221处被强烈氧化的高趋势，Cys 221在氧化结构中变成半胱氨酸磺酸残基。其天然结构仅在三（2-羧乙基）膦存在下获得。这种氧化可能是对位于Cys位点的第二个Zn的亲和力较低的结果，这也解释了观察到的Vim-2对螯合剂的敏感性。这种修饰，如果存在于自然界中，可能在催化下调中发挥作用。进行天然和氧化的Vim-2与Vim-1的预测模型（其显示与Vim-2相比在Cys位点中的一个残基不同）之间的比较，以解释不同的活性和抗生素特异性。(c)2007爱思唯尔有限公司保留所有权利。
The crystal structures of the universally widespread metallo-beta-lactamase (MBL) Verona integron-encoded MBL (VIM)-2 from Pseudomonas aeruginosa have been solved in their native form as well as in an unexpected oxidised form. This carbapenem-hydrolysing enzyme belongs to the so-called 131 subfamily of MBLs and shares the folding of alpha beta/beta alpha sandwich, consisting of a core of beta-sheet surrounded by alpha-helices. Surprisingly, it showed a high tendency to be strongly oxidised at the catalytic cysteine located in the Cys site, Cys221, which, in the oxidised structure , becomes a cysteinesulfonic residue. Its native structure was obtained only in the presence of Tris(2-carboxyethyl)phosphine. This oxidation might be a consequence of a lower affinity for the second Zn located in the Cys site that would also explain the observed susceptibility of VIM-2 to chelating agents. This modification, if present in nature, might play a role in catalytic down-regulation. Comparison between native and oxidised VIM-2 and a predicted model of VIM-1 (which shows one residue different in the Cys site compared with VIM-2) is performed to explain the different activities and antibiotic specificities. (c) 2007 Elsevier Ltd. All rights reserved.