Focus on molecules: maspin.
Focus on molecules: maspin.
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DOI：
10.1016/j.exer.2009.07.003
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发表时间：
2010-01
影响因子：
3.4
通讯作者：
Twining, Sally
中科院分区：
文献类型：
--
作者：
Narayan, Malathi;Twining, Sally
乳腺丝氨酸蛋白酶抑制剂或maspin（GenBank登录号：U 04313; RefSeq ID：NM_002639; PDB ID：1xqj，1xqg，1 wz 9，1xu 8）是丝氨酸蛋白酶抑制剂（丝氨酸蛋白酶抑制剂）的卵清蛋白进化枝的42 kDa、非经典、非抑制性成员。在人类中，编码maspin的基因位于染色体18上，在含有其他丝氨酸蛋白酶抑制剂基因的簇中，如鳞状细胞癌抗原（SCCA）1和2和纤溶酶原激活物抑制剂2型（派-2）。使用正常和恶性乳腺上皮细胞mRNA产生的cDNA，通过消减杂交研究鉴定了Maspin（Zou et al. 1994）。而正常乳腺组织的肌上皮细胞表达maspin，其表达在转移性乳腺肿瘤细胞下调。Maspin在人乳腺上皮细胞中被分类为II类肿瘤抑制基因，因为尽管其表达在许多转移性癌细胞中下调，但其不突变。虽然maspin在结构上类似于经典的抑制性丝氨酸蛋白酶抑制剂，但反应位点（或中心）环（RSL或RCL）在RSL的N末端具有非标准铰链区，这阻止了它从应力（S）到松弛（R）状态的关键结构变化（图1）。Maspin由9个α-螺旋（螺旋A-I）和3个β-折叠（折叠AC）组成，采用天然丝氨酸蛋白酶抑制剂折叠，RSL完全从蛋白质体中排出（图1）。maspin的RSL在长度、结构和位置上是独特的。虽然RSL暴露并被一些蛋白酶切割，但它以未切割的形式发挥作用。RSL与分子的其余部分几乎没有接触，并且如通过低电子密度所观察到的那样非常灵活。一个不寻常的凸起是由D和E α-螺旋区域内的一个埋藏盐桥引起的，在许多其他丝氨酸蛋白酶抑制剂中，该区域对辅因子识别很重要。此外，完整maspin可在G α-螺旋和相邻序列中发生主要构象变化，在"开放“和”闭合“构象之间转换，从而改变分子假定辅因子结合表面的静电性质，这可能影响分子的功能（Law et al. 2005）。
Mammary Serine Protease Inhibitor or maspin (GenBank Accession Number: U04313; RefSeq ID: NM_002639; PDB ID: 1xqj, 1xqg, 1wz9, 1xu8) is a 42 kDa, non-classical, non-inhibitory member of the ovalbumin clade of serine protease inhibitors (serpins). In humans, the gene encoding maspin is located on chromosome 18 in a cluster containing genes for other serpins such as squamous cell carcinoma antigen (SCCA) 1 and 2 and plasminogen activator inhibitor type 2 (PAI-2). Maspin was identified from subtractive hybridization studies using cDNAs produced from mRNA of normal and malignant mammary epithelial cells (Zou et al. 1994). While myoepithelial cells of normal mammary tissue expressed maspin, its expression was down-regulated in metastatic mammary tumor cells. Maspin was classified as a class II tumor suppressor gene in human mammary epithelial cells because although its expression is downregulated in many metastatic carcinoma cells, it is not mutated. Although maspin resembles classical inhibitory serpins in structure, the reactive site (or center) loop (RSL or RCL) possesses a non-standard hinge region, on the N-terminus of the RSL, which prevents it from undergoing a critical structural change from the stressed (S) to relaxed (R) state (Fig. 1). This prevents maspin from being able to trap and inhibit serine proteases.Maspin consists of nine α-helices (helix A-I) and three β-sheets (sheet AC) and adopts the native serpin fold with the RSL fully expelled from the body of the protein (Fig. 1). The RSL of maspin is unique in length, structure and position. Although the RSL is exposed and cleaved by some proteases, it functions in the uncleaved form. The RSL makes very little contact with the rest of the molecule and is very flexible as observed by low electron density. An unusual bulge is caused by a buried salt bridge in the region of the D and E α-helices, an area shown in many other serpins to be important for co-factor recognition. Additionally, intact maspin can undergo a major conformational change in the G α-helix and adjacent sequences, switching between an ‘open’and ‘closed’conformation thereby altering the electrostatic properties of a presumptive co-factor binding surface of the molecule, which may affect the function of the molecule (Law et al. 2005).
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影响因子：
4.8
作者：
Ngamkitidechakul, C;Warejcka, DJ;Twining, SS
通讯作者：
Twining, SS
影响因子：
3.4
作者：
Horswill, Mark A.;Narayan, Malathi;Twining, Sally S.
通讯作者：
Twining, Sally S.
影响因子：
4.8
作者：
Law, RHP;Irving, JA;Whisstock, JC
通讯作者：
Whisstock, JC
影响因子：
56.9
作者：
ZOU, ZQ;ANISOWICZ, A;SAGER, R
通讯作者：
SAGER, R