Alanine:glyoxylate aminotransferase peroxisome-to-mitochondrion mistargeting in human hereditary kidney stone disease

被引：31

作者：

Danpure, CJ ^{[1
]}

Lumb, MJ ^{[1
]}

Birdsey, GM ^{[1
]}

Zhang, XX ^{[1
]}

机构：

[1] UCL, Dept Biol, London WC1E 6BT, England

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS | 2003年 / 1647卷 / 1-2期

关键词：

alanine : glyoxylate aminotransferase; primary hyperoxaluria type 1; peroxisomal protein targeting; mitochondrial protein targeting; kidney stone; human genetic disease;

D O I：

10.1016/S1570-9639(03)00055-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The pyridoxal-phosphate (PLP)-dependent enzyme alanine:glyoxylate aminotransferase (AGT) is mistargeted from peroxisomes to mitochondria in patients with the hereditary kidney stone disease primary hyperoxaluria type I (PHI) due to the synergistic interaction between a common Pro(11) Leu polymorphism and a PH1-specific Gly(170) Arg mutation. The kinetic partitioning of newly synthesised AGT between peroxisomes and mitochondria is determined by the combined effects of (1) the generation of cryptic mitochondrial targeting information, and (2) the inhibition of AGT dimerization. The crystal structure of AGT has recently been solved, allowing the effects of the various polymorphisms and mutations to be rationalised in terms of AGT's three-dimensional conformation. Procedures that increase dimer stability and/or increase the rate of dimer formation have potential in the formulation of novel strategies to treat this otherwise intractable life-threatening disease. (C) 2003 Elsevier Science B.V. All rights reserved.

引用

页码：70 / 75

页数：6

共 45 条

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