Disulfide between Cys392 and Cys438 of human serum albumin IS redox-active, which is responsible for the thioredoxin-supported lipid peroxidase activity
Disulfide between Cys392 and Cys438 of human serum albumin IS redox-active, which is responsible for the thioredoxin-supported lipid peroxidase activity
复制标题
DOI：
10.1016/j.abb.2005.09.022
复制
发表时间：
2006-01-01
影响因子：
3.9
通讯作者：
Kim, IH
中科院分区：
文献类型：
--
作者：
Cha, MK;Kim, IH
人血清白蛋白（HSA）是一种存在于血浆和细胞外液中的丰富蛋白质。以前，我们发现，HSA有一个独特的硫氧还蛋白（Trx）依赖的脂质过氧化物酶活性的棕榈酰辅酶A的存在下。在本文中，我们确定了氧化还原活性的二硫化物，这可以特异性地被Trx还原，负责Trx依赖的脂质过氧化物酶活性。HSA的IIB-III片段（Pro299-Leu 585）维持Trx依赖的脂质过氧化物酶活性。用硫醇特异性修饰剂对Trx还原的IIB-III进行化学修饰导致过氧化物酶活性完全丧失。来自失活的HSA和IIB-III的胰蛋白酶肽的分析表明，Cys 392和Cys 438，这存在于HSA的胞内二硫键，优先在HSA和IIB-III的修改。综上所述，这些结果表明，HSA具有使用Trx作为体内电子供体来还原脂质过氧化氢的能力，并且Cys 392和Cys 438之间的氧化还原活性二硫化物充当Trx连接的脂质过氧化物酶活性的催化的主要位点。(c)2005年爱思唯尔公司All rights reserved.
Human serum albumin (HSA) is an abundant protein found in blood plasma and extracellular fluids. Previously, we found that HSA has a distinct thioredoxin (Trx)-dependent lipid peroxidase activity in the presence of palmitoyl-CoA. In this paper, we identified the redox-active disulfide, which can be specifically reduced by Trx, responsible for the Trx-dependent lipid peroxidase activity. The IIB-III fragment of HSA (Pro299-Leu585) sustained the Trx-dependent lipid peroxidase activity. Chemical modification of the Trx-reduced IIB-III with a thiol-specific modification agent resulted in a complete loss or the peroxidase activity. The analysis of tryptic-peptides derived from the inactivated HSA and IIB-III revealed that Cys392 and Cys438, which exist as an intramlecular disulfide bond in HSA, were preferentially modified in both HSA and IIB-III. Taken together, these results suggested that HSA has a capability to reduce lipid hydroperoxide with the use of Trx as an in vivo electron donor, and that the redox-active disulfide between Cys392 and Cys438 acts as a primary site of the catalysis for the Trx-linked lipid peroxidase activity. (c) 2005 Elsevier Inc. All rights reserved.