Comparison of enzymatic properties between hPADI2 and hPADI4
Comparison of enzymatic properties between hPADI2 and hPADI4
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DOI：
10.1016/j.bbrc.2004.11.152
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发表时间：
2005-02-04
影响因子：
3.1
通讯作者：
Yamamoto, K
中科院分区：
文献类型：
--
作者：
Nakayama-Hamada, M;Suzuki, A;Yamamoto, K
在类风湿性关节炎 (RA) 患者的血清中，发现针对瓜氨酸蛋白的自身抗体对 RA 具有高度特异性。肽基精氨酸脱亚胺酶 (PADI) 是负责蛋白质瓜氨酸化的酶。在许多 PADI 亚型中，只有 PADI4 被确定为 RA 易感基因。为了了解 RA 发生和进展的机制，我们比较了 RA 患者滑膜组织中存在的两种 PADI（人 PADI2 和人 PADI4）的特性。我们确认了它们在 RA 滑膜中的精确分布，并比较了稳定性、Ca2+ 依赖性、最佳 pH 范围和底物特异性。 hPADI2 和 hPADI4 之间的上述特性存在微小但显着的差异。使用 LC/MS/MS 分析，我们鉴定了人纤维蛋白原中的序列，表明 hPADI2 和 hPADI4 以不同的方式进行瓜氨酸化。我们的结果表明hPADI2和hPADI4在生理和病理条件下具有不同的作用。需要进一步研究以更好地了解 hPADI 在 RA 发生和进展中的作用。 (C) 2004 Elsevier Inc. 保留所有权利。
In the sera of rheumatoid arthritis (RA) patients, autoantibodies directed to citrullinated proteins are found with high specificity for RA. Peptidylarginine deiminases (PADIs) are enzymes responsible for protein citrullination. Among many isoforms of PADIs, only PADI4 has been identified as an RA-susceptibility gene. To understand the mechanisms of the initiation and progression of RA, we compared the properties of two PADIs, human PADI2 and human PADI4, which are present in the synovial tissues of RA patients. We confirmed their precise distribution in the RA synovium and compared the stability, Ca2+ dependency, optimal pH range, and substrate specificity. Small but significant differences were found in the above-mentioned properties between hPADI2 and hPADI4. Using LC/MS/MS analysis, we identified the sequences in human fibrinogen indicating that hPADI2 and hPADI4 citrullinate in different manners. Our results indicate that hPADI2 and hPADI4 have different roles under physiological and pathological conditions. Further studies are needed for the better understanding of the role of hPADIs in the initiation and progression of RA. (C) 2004 Elsevier Inc. All rights reserved.