The crystal structure of SdsA1, an alkylsulfatase from Pseudomonas aeruginosa, defines a third class of sulfatases

The crystal structure of SdsA1, an alkylsulfatase from Pseudomonas aeruginosa, defines a third class of sulfatases
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DOI:
10.1073/pnas.0510501103
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发表时间:
2006-05-16
影响因子:
11.1
通讯作者:
Schubert, Wolf-Dieter
Schubert, Wolf-Dieter
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hagelueken, Gregor;Adams, Thorsten M.;Schubert, Wolf-Dieter

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铜绿假单胞菌既是一种普遍存在的环境细菌,也是一种条件致病菌。显著的新陈代谢多功能性使它能够占据大量的生态位,包括废水处理厂和人类呼吸道等恶劣环境。铜绿假单胞菌能够降解和代谢大多数商业个人卫生产品的洗涤剂生物化学十二烷基硫酸钠。我们确定SclsAll of A铜绿假单胞菌是一种分泌型SID水解酶,它允许细菌使用初级硫酸盐,如十二烷基硫酸钠作为唯一的碳源或硫源。SdsA1的同源物存在于许多致病细菌和一些非致病细菌中。SdsA1的晶体结构显示了三个不同的结构域。具有双核锌离子簇的N-末端催化结构域是金属-β-内酰胺酶折叠家族的一个独特的成员,中心二聚结构域确保了对高浓度SID的抵抗,而C-末端结构域提供了疏水沟槽,可能是为了招募长长的脂类底物。Apo-SdsAl及其与底物类似物和产物的络合物的晶体结构表明,锌离子簇合物间接激活了水分子,这是一种酶机制。因此,SclsAl酶代表了一类以前没有描述过的硫酸盐酶,它允许铜绿假单胞菌在其他杀菌条件下存活并茁壮成长。
Pseudomonas aeruginosa is both a ubiquitous environmental bacterium and an opportunistic human pathogen. A remarkable metabolic versatility allows it to occupy a multitude of ecological niches, including wastewater treatment plants and such hostile environments as the human respiratory tract. P. aeruginosa is able to degrade and metabolize biocidic SDS, the detergent of most commercial personal hygiene products. We identify SclsAll of A aeruginosa as a secreted SIDS hydrolase that allows the bacterium to use primary sulfates such as SDS as a sole carbon or sulfur source. Homologues of SdsA1 are found in many pathogenic and some nonpathogenic bacteria. The crystal structure of SdsA1 reveals three distinct domains. The N-terminal catalytic domain with a binuclear Zn2+ cluster is a distinct member of the metallo-beta-lactamase fold family, the central dimerization domain ensures resistance to high concentrations of SIDS, whereas the C-terminal domain provides a hydrophobic groove, presumably to recruit long aliphatic substrates. Crystal structures of apo-SdsAl and complexes with substrate analog and products indicate an enzymatic mechanism involving a water molecule indirectly activated by the Zn2+ cluster. The enzyme SclsAl thus represents a previously undescribed class of sulfatases that allows A aeruginosa to survive and thrive under otherwise bacteriocidal conditions.