Latent LytM at 1.3 A resolution
Latent LytM at 1.3 A resolution
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DOI：
10.1016/j.jmb.2003.11.009
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发表时间：
2004-01-16
影响因子：
5.6
通讯作者：
Bochtler, M
中科院分区：
文献类型：
--
作者：
Odintsov, SG;Sabala, I;Bochtler, M
来自金黄色葡萄球菌的自溶素LytM是具有特征性HxH基序的Zn 2+依赖性甘氨酰甘氨酸内肽酶，其属于溶葡萄球菌酶型（MEROPS M23/37）金属肽酶。在这里，我们提出了1.3埃晶体结构的LytM，第一结构的溶葡萄球菌酶型肽酶。在LytM结构中，Zn 2+通过N117、H210、D214和H293（HxH基序的第二个组氨酸）的侧链四面体配位。虽然接近活性位点，HxH基序的第一个组氨酸H291不直接参与Zn 2 +-配位，并且在Zn 2+的配位球中没有水分子，这表明晶体结构显示了酶的潜在形式。虽然LytM以前没有被认为是一种酶原，我们表明，LytM的截短版本，缺乏保守性差的Zn 2+配体N117的N-末端部分具有比全长酶高得多的比活性。这一观察结果与已知的其他溶葡萄球菌酶型蛋白中前片段的去除以及先前在S.金黄色葡萄球菌上清液。LytM中的“天冬酰胺开关”类似于前基质金属蛋白酶中的“半胱氨酸开关”。(C)2003 Elsevier Ltd.保留所有权利。
LytM, an autolysin from Staphylococcus aureus, is a Zn2+-dependent glycylglycine endopeptidase with a characteristic HxH motif that belongs to the lysostaphin-type (MEROPS M23/37) of metallopepticlases. Here, we present the 1.3 Angstrom crystal structure of LytM, the first structure of a lysostaphin-type peptidase. In the LytM structure, the Zn2+ is tetrahedrally coordinated by the side-chains of N117, H210, D214 and H293, the second histidine of the HxH motif. Although close to the active-site, H291, the first histidine of the HxH motif, is not directly involved in Zn2+-ordination, and there is no water molecule in the coordination sphere of the Zn2+, suggesting that the crystal structure shows a latent form of the enzyme. Although LytM has not previously been considered as a proenzyme, we show that a truncated version of LytM that lacks the N-terminal part with the poorly conserved Zn2+ ligand N117 has much higher specific activity than full-length enzyme. This observation is consistent with the known removal of profragments in other lysostaphintype proteins and with a prior observation of an active LytM degradation fragment in S. aureus supernatant. The "asparagine switch" in LytM is analogous to the "cysteine switch" in pro-matrix metalloproteases. (C) 2003 Elsevier Ltd. All rights reserved.