Structure of Escherichia coli lytic transglycosylase MltA with bound chitohexaose -: Implications for peptidoglycan binding and cleavage
Structure of Escherichia coli lytic transglycosylase MltA with bound chitohexaose -: Implications for peptidoglycan binding and cleavage
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DOI：
10.1074/jbc.m701818200
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发表时间：
2007-07-20
影响因子：
4.8
通讯作者：
Thunnissen, Andy-Mark W. H.
中科院分区：
文献类型：
--
作者：
van Straaten, Karin E.;Barends, Thomas R. M.;Thunnissen, Andy-Mark W. H.
一个无活性的突变体（D308 A）的裂解转糖基酶MltA从大肠杆菌的晶体结构已被确定在两个不同的apo-形式，以及在复杂的底物类似物chitohexaose。壳六糖与活性位点沟中的所有六个糖残基结合，在键裂解中心具有完整的糖苷键。其结合诱导MltA中两个结构域的大的重新取向，使活性位点沟变窄，并允许寡糖与来自两个结构域的残基的紧密相互作用。这些结构鉴定了MltA中在肽聚糖结合和识别中具有关键作用的残基，并证实Asp-308是单一催化残基，充当一般酸/碱。此外，这些结构表明催化涉及易分裂的糖苷键的高能构象，并且推定的氧碳正离子中间体通过附近α螺旋的偶极矩来稳定。
Crystal structures of an inactive mutant (D308A) of the lytic transglycosylase MltA from Escherichia coli have been determined in two different apo-forms, as well as in complex with the substrate analogue chitohexaose. The chitohexaose binds with all six saccharide residues in the active site groove, with an intact glycosidic bond at the bond cleavage center. Its binding induces a large reorientation of the two structural domains in MltA, narrowing the active site groove and allowing tight interactions of the oligosaccharide with residues from both domains. The structures identify residues in MltA with key roles in the binding and recognition of peptidoglycan and confirm that Asp-308 is the single catalytic residue, acting as a general acid/base. Moreover, the structures suggest that catalysis involves a high energy conformation of the scissile glycosidic linkage and that the putative oxocarbenium ion intermediate is stabilized by the dipole moment of a nearby alpha-helix.