• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

在法布里病和周期性自身炎症性神经病变期间对吡啉和14-3-3蛋白调节的计算机模拟研究

In Silico Study of Pyrin and 14-3-3 Protein Modulation During FMF and PAAND.

作者信息

Paronyan Adrine, Muradyan Nelli, Sargsyan Arsen, Arakelov Vahram, Arakelov Grigor, Nazaryan Karen

机构信息

Institute of Molecular Biology of the National Academy of Sciences of the Republic of Armenia (NAS RA), Yerevan 0014, Armenia.

Russian-Armenian (Slavonic) University, Yerevan 0051, Armenia.

出版信息

ACS Omega. 2025 Jan 23;10(4):3462-3473. doi: 10.1021/acsomega.4c07386. eCollection 2025 Feb 4.

DOI:10.1021/acsomega.4c07386
PMID:39926484
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11799992/
Abstract

Familial Mediterranean fever (FMF) is a genetically determined disease transmitted through autosomal recessive inheritance. Recently, a rare but similar disease to FMF, pyrin-associated autoinflammation with neutrophilic dermatosis (PAAND), has been discovered. PAAND is inherited dominantly and is characterized by neutrophilic dermatosis and recurrent fevers. The cause of the disease is point mutations in the MEFV gene. The pyrin protein is a product of this gene and is one of the main factors in the disease's progression. This paper examines the interaction between pyrin and the 14-3-3 protein and screens for modulators affecting their interaction. Regulating this interaction is crucial for understanding the mechanism of FMF development, specifically the disruption of this complexation, which leads to inflammatory responses. The pyrin-14-3-3 interaction is essential for designing potential drugs since weakening this interaction can result in inflammation. This research of in silico experiments identified low molecular weight chemical compounds that have a modulating effect on the tertiary structures of mutant variations of pyrin and 14-3-3 proteins. Studies have identified modulator molecules that interact with the FMF-associated mutant structure of pyrin (M694I) and 14-3-3τ. The chemical compounds that result from this process can be used as modulators and as a potential new basis for the development of therapeutic drugs.

摘要

家族性地中海热（FMF）是一种通过常染色体隐性遗传传播的基因决定疾病。最近，一种与FMF罕见但相似的疾病——伴有嗜中性皮病的吡啉相关自身炎症（PAAND）被发现。PAAND以显性方式遗传，其特征为嗜中性皮病和反复发热。该疾病的病因是MEFV基因中的点突变。吡啉蛋白是该基因的产物，是疾病进展的主要因素之一。本文研究了吡啉与14-3-3蛋白之间的相互作用，并筛选影响它们相互作用的调节剂。调节这种相互作用对于理解FMF的发病机制至关重要，特别是这种复合物形成的破坏会导致炎症反应。由于减弱这种相互作用会引发炎症，因此吡啉-14-3-3相互作用对于设计潜在药物至关重要。这项计算机模拟实验研究确定了对吡啉和14-3-3蛋白突变变体的三级结构具有调节作用的低分子量化合物。研究已经确定了与吡啉（M694I）和14-3-3τ的FMF相关突变结构相互作用的调节分子。这一过程产生的化合物可用作调节剂，并作为治疗药物开发的潜在新基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/2e3fdc05be7b/ao4c07386_0016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/6fa000472d78/ao4c07386_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/77ffb2048a07/ao4c07386_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/88c7defa0d03/ao4c07386_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/d86790cd0f6e/ao4c07386_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/ea1d3124484c/ao4c07386_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/7eea08bbd83f/ao4c07386_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/3a2f898d886d/ao4c07386_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/a6dae6589461/ao4c07386_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/c47a7cfff108/ao4c07386_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/6c156f66e0ed/ao4c07386_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/ea4aec842b86/ao4c07386_0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/8f509b4ba542/ao4c07386_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/824fecdc8dd3/ao4c07386_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/b18210e8d47b/ao4c07386_0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/c09b71414828/ao4c07386_0015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/2e3fdc05be7b/ao4c07386_0016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/6fa000472d78/ao4c07386_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/77ffb2048a07/ao4c07386_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/88c7defa0d03/ao4c07386_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/d86790cd0f6e/ao4c07386_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/ea1d3124484c/ao4c07386_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/7eea08bbd83f/ao4c07386_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/3a2f898d886d/ao4c07386_0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/a6dae6589461/ao4c07386_0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/c47a7cfff108/ao4c07386_0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/6c156f66e0ed/ao4c07386_0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/ea4aec842b86/ao4c07386_0014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/8f509b4ba542/ao4c07386_0011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/824fecdc8dd3/ao4c07386_0012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/b18210e8d47b/ao4c07386_0013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/c09b71414828/ao4c07386_0015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90a1/11799992/2e3fdc05be7b/ao4c07386_0016.jpg

相似文献

1
In Silico Study of Pyrin and 14-3-3 Protein Modulation During FMF and PAAND.在法布里病和周期性自身炎症性神经病变期间对吡啉和14-3-3蛋白调节的计算机模拟研究
ACS Omega. 2025 Jan 23;10(4):3462-3473. doi: 10.1021/acsomega.4c07386. eCollection 2025 Feb 4.
2
A novel Pyrin-Associated Autoinflammation with Neutrophilic Dermatosis mutation further defines 14-3-3 binding of pyrin and distinction to Familial Mediterranean Fever.一种新的伴有嗜中性皮肤病的与 Pyrin 相关的自身炎症突变进一步明确了 Pyrin 的 14-3-3 结合以及与家族性地中海热的区别。
Ann Rheum Dis. 2017 Dec;76(12):2085-2094. doi: 10.1136/annrheumdis-2017-211473. Epub 2017 Aug 23.
3
Homozygous MEFV Gene Variant and Pyrin-Associated Autoinflammation With Neutrophilic Dermatosis: A Family With a Novel Autosomal Recessive Mode of Inheritance.纯合 MEFV 基因突变与伴嗜中性皮病的甲硫氨酰-脑啡肽酶相关自身炎症：一个具有新型常染色体隐性遗传方式的家系。
JAMA Dermatol. 2021 Dec 1;157(12):1466-1471. doi: 10.1001/jamadermatol.2021.3899.
4
Phenotypical and Functional Characterization of Neutrophils in Two Pyrin-Associated Auto-inflammatory Diseases.两种吡喃相关自身炎症性疾病中性粒细胞的表型和功能特征。
J Clin Immunol. 2021 Jul;41(5):1072-1084. doi: 10.1007/s10875-021-01008-4. Epub 2021 Mar 5.
5
Functional Assessment of Disease-Associated Pyrin Variants.疾病相关 Pyrin 变异体的功能评估。
Methods Mol Biol. 2022;2523:179-195. doi: 10.1007/978-1-0716-2449-4_12.
6
New Diseases Linked to MEFV Variants or Pyrinopathies.与MEFV基因变异或热蛋白病相关的新疾病。
J Allergy Clin Immunol Pract. 2025 Mar;13(3):522-532. doi: 10.1016/j.jaip.2024.12.022. Epub 2024 Dec 24.
7
The genetic basis of autosomal dominant familial Mediterranean fever.常染色体显性遗传性家族性地中海热的遗传基础。
QJM. 2000 Apr;93(4):217-21. doi: 10.1093/qjmed/93.4.217.
8
Steroid hormone catabolites activate the pyrin inflammasome through a non-canonical mechanism.甾体激素代谢物通过非经典机制激活吡喃炎性小体。
Cell Rep. 2022 Oct 11;41(2):111472. doi: 10.1016/j.celrep.2022.111472.
9
MEFV mutation analysis of familial Mediterranean fever in Japan.日本家族性地中海热的MEFV基因突变分析。
Clin Exp Rheumatol. 2008 Jan-Feb;26(1):13-7.
10
Function and mechanism of the pyrin inflammasome.pyrin 炎症小体的功能和机制。
Eur J Immunol. 2018 Feb;48(2):230-238. doi: 10.1002/eji.201746947. Epub 2017 Dec 6.

本文引用的文献

1
Crystal structure and ligandability of the 14-3-3/pyrin interface.14-3-3/吡喃复合物的晶体结构和配体结合能力。
Biochem Biophys Res Commun. 2023 Apr 9;651:1-7. doi: 10.1016/j.bbrc.2023.02.013. Epub 2023 Feb 4.
2
Computational approaches for the design of modulators targeting protein-protein interactions.针对靶向蛋白质-蛋白质相互作用的调节剂设计的计算方法。
Expert Opin Drug Discov. 2023 Mar;18(3):315-333. doi: 10.1080/17460441.2023.2171396. Epub 2023 Feb 23.
3
The trRosetta server for fast and accurate protein structure prediction.
TrRosetta 服务器：用于快速准确的蛋白质结构预测。
Nat Protoc. 2021 Dec;16(12):5634-5651. doi: 10.1038/s41596-021-00628-9. Epub 2021 Nov 10.
4
Use of molecular docking computational tools in drug discovery.在药物发现中使用分子对接计算工具。
Prog Med Chem. 2021;60:273-343. doi: 10.1016/bs.pmch.2021.01.004. Epub 2021 May 27.
5
Analyzing FDA-approved drugs for compliance of pharmacokinetic principles: should there be a critical screening parameter in drug designing protocols?分析美国食品药品监督管理局（FDA）批准的药物是否符合药代动力学原理：药物设计方案中是否应该有一个关键筛选参数？
Expert Opin Drug Metab Toxicol. 2021 Apr;17(4):351-354. doi: 10.1080/17425255.2021.1865309. Epub 2020 Dec 29.
6
14-3-3 modulation of the inflammatory response.14-3-3 调节炎症反应。
Pharmacol Res. 2021 Jan;163:105236. doi: 10.1016/j.phrs.2020.105236. Epub 2020 Oct 11.
7
The Pyrin Inflammasome in Health and Disease.Pyrin 炎症小体在健康与疾病中的作用
Front Immunol. 2019 Aug 7;10:1745. doi: 10.3389/fimmu.2019.01745. eCollection 2019.
8
TTClust: A Versatile Molecular Simulation Trajectory Clustering Program with Graphical Summaries.TTClust：一个功能多样的分子模拟轨迹聚类程序，带有图形摘要。
J Chem Inf Model. 2018 Nov 26;58(11):2178-2182. doi: 10.1021/acs.jcim.8b00512. Epub 2018 Oct 30.
9
Complex formation dynamics of native and mutated pyrin's B30.2 domain with caspase-1.天然和突变的pyrin 的 B30.2 结构域与 caspase-1 的复合物形成动力学。
Proteins. 2018 Jun;86(6):676-683. doi: 10.1002/prot.25494. Epub 2018 Apr 1.
10
SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules.SwissADME：一个免费的网络工具，用于评估小分子的药代动力学、类药性和药物化学友善性。
Sci Rep. 2017 Mar 3;7:42717. doi: 10.1038/srep42717.