Similar active sites in lysostaphins and D-Ala-D-Ala metallopeptidases
Similar active sites in lysostaphins and D-Ala-D-Ala metallopeptidases
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DOI：
10.1110/ps.03515704
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发表时间：
2004-04-01
期刊：
影响因子：
8
通讯作者：
Sabala, I
中科院分区：
文献类型：
--
作者：
Bochtler, M;Odintsov, SG;Sabala, I
几乎肽聚糖中的每一个酰胺键都有特定的肽酶存在。在一些情况下，具有不同特异性的肽聚糖水解酶家族被证明是相关的。在此我们表明，溶葡萄球菌素型肽酶和D -丙氨酸 - D -丙氨酸金属肽酶具有相似的活性位点，并且在其他方面差异很大的折叠结构中共享一个核心折叠基序。中心的锌离子（Zn²⁺）由两个组氨酸、一个天冬氨酸和一个水分子进行四面体配位。锌离子螯合残基在所有序列中按照组氨酸、天冬氨酸、组氨酸的顺序出现，并且分别通过Nε、Oδ和Nδ与金属离子接触。其他活性位点残基的特性各不相同，但在除VanX之外所有已知结构的酶中，在与锌离子结合的第二个组氨酸配体上游两个残基处存在一个保守的组氨酸。由于在音猬因子的N末端隐蔽肽酶结构域中也发现了活性位点残基的相同排列方式，我们建议将这种活性位点残基的排列方式称为“LAS”排列，因为它存在于溶葡萄球菌素型酶、D -丙氨酸 - D -丙氨酸金属肽酶以及音猬因子N结构域中的隐蔽肽酶中。
Specific peptidases exist for nearly every amide linkage in peptidoglycan. In several cases, families of peptidoglycan hydrolases with different specificities turned out to be related. Here we show that lysostaphin-type peptidases and D-Ala-D-Ala metallopeptidases have similar active sites and share a core folding motif in otherwise highly divergent folds. The central Zn2+, is tetrahedrally coordinated by two histidines, an aspartate, and a water molecule. The Zn2+, chelating residues occur in the order histidine, aspartate, histidine in all sequences and contact the metal via the Nepsilon, the Odelta, and the Ndelta, respectively. The identity of the other active-site residues varies, but in all enzymes of known structure except for VanX, a conserved histidine is present two residues upstream of the second histidine ligand to the Zn2+. As the same arrangement of active-site residues is also found in the N-terminal, cryptic peptidase domain of sonic hedgehog, we propose that this arrangement of active-site residues be called the "LAS" arrangement, because it is present in lysostaphin-type enzymes, D-Ala-D-Ala metallopeptidases, and in the cryptic peptidase in the N-domain of sonic hedgehog.