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缺氧誘導因子脯胺酸羥化酶

維基百科,自由的百科全書
Hypoxia-inducible factor-proline dioxygenase
識別碼
EC編號 1.14.11.29
數據庫
IntEnz IntEnz瀏覽
BRENDA英語BRENDA BRENDA入口
ExPASy英語ExPASy NiceZyme瀏覽
KEGG KEGG入口
MetaCyc英語MetaCyc 代謝路徑
PRIAM英語PRIAM_enzyme-specific_profiles 概述
PDB RCSB PDB PDBj PDBe PDBsum

HIF脯胺酸羥化酶(英語:HIF prolyl-hydroxylase)是一個包含在缺氧誘導因子(英語:Hypoxia-inducible factor,簡稱:HIF)訊息路徑中的酶,也是一系列稱為HIF脯胺酸羥化酶抑制劑 治療性藥物的目標

缺氧誘導因子(HIF)是一個在演化上被保留下來的轉錄因子[1],它讓細胞可以針對低氧濃度環境作出生理性的反應[2]。其中一種特定作用在HIF上的脯胺酸羥化酶已經被確認存在;[3]而羥基化的HIF能讓蛋白質被作為降解的目標[3]

HIF脯胺酸羥化酶已經被各式各樣抑制劑作為目標,用來治療中風[4],腎臟疾病[5]缺血[6]貧血[7],和其他重大疾病。在紅血球過多症相關以及乳癌相關的PHD2突變的案例中,臨床觀察下的脯胺酸羥化酶區域突變會影響它對HIF受質的選擇性,這點對藥物設計有重要的意義[8] 。 在人體中,HIF脯胺酸雙氧化酶有三種種型。分別是 PHD1、PHD2和PHD3。其中,PHD2因為它對氧氣緩慢的反應速度而被視為人體最重要的氧氣感應器[9]

參考文獻

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  8. ^ Chowdhury, Rasheduzzaman; Leung, Ivanhoe K. H.; Tian, Ya-Min; Abboud, Martine I.; Ge, Wei; Domene, Carmen; Cantrelle, François-Xavier; Landrieu, Isabelle; Hardy, Adam P. Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases. Nature Communications. 2016-08-26, 7: 12673. PMC 5007464可免費查閱. PMID 27561929. doi:10.1038/ncomms12673 (英語). 
  9. ^ Berra E, Benizri E, Ginouvès A, Volmat V, Roux D, Pouysségur J. HIF prolylhydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1α in normoxia. EMBO J. Aug 2003, 22 (16): 4082–4090. PMC 175782可免費查閱. PMID 12912907. doi:10.1093/emboj/cdg392.