美国印第安那大学和斯坦福大学的医学院的研究人员发现了一类新的“化学分子伴侣(chemical chaperone)”，这种物质能够恢复某些发生突变的酶的功能。该研究发表在1月10日的Nature Structural & Molecular Biology杂志上，在该报告中，他们描述了这种化学物质如何在机体中发挥作用的过程，这项发现或有助于开发新的药物，治疗因心脏病发作引起的肌肉损伤。
这项研究由印第安纳大学Thomas Hurley博士主持，研究发现，一种命名为Alda-1的化学物质能够修复发生突变的ALDH2酶的功能。ALDH2酶对酒精代谢或因心脏病发作缺氧所产生的毒素的代谢有重要作用。
但是在一些人群(如40%的亚洲裔人群)中，ALDH2酶是以一种突变体的形式存在于机体中。携带突变体ALDH2酶的人群其患心血管损伤的风险比正常人更大。（生物谷Bioon.com）
该研究组曾在2008年Science杂志上报道，Alda-1可绕过机体一般的信号系统直接激活ALDH2酶，从而降低心肌组织损伤。在最近的这项研究报告中，描述了Alda-1如何激活ALDH2酶的过程。研究人员将这个过程比喻成一个“木工工艺”过程，Alda-1的作用类似于一个楔子，可以结合到ALDH2酶的一个关键位点，从而使酶恢复正常功能。详情见：Science ：心脏的损伤控制
生物谷推荐原始出处：
Nature Structural & Molecular Biology 10 January 2010 | doi:10.1038/nsmb.1737
Alda-1 is an agonist and chemical chaperone for the common human aldehyde dehydrogenase 2 variant
Samantha Perez-Miller1, Hina Younus1, Ram Vanam1, Che-Hong Chen2, Daria Mochly-Rosen2 & Thomas D Hurley1
In approximately one billion people, a point mutation inactivates a key detoxifying enzyme, aldehyde dehydrogenase (ALDH2). This mitochondrial enzyme metabolizes toxic biogenic and environmental aldehydes, including the endogenously produced 4-hydroxynonenal (4HNE) and the environmental pollutant acrolein, and also bioactivates nitroglycerin. ALDH2 is best known, however, for its role in ethanol metabolism. The accumulation of acetaldehyde following the consumption of even a single alcoholic beverage leads to the Asian alcohol-induced flushing syndrome in ALDH2*2 homozygotes. The ALDH2*2 allele is semidominant, and heterozygotic individuals show a similar but less severe phenotype. We recently identified a small molecule, Alda-1, that activates wild-type ALDH2 and restores near-wild-type activity to ALDH2*2. The structures of Alda-1 bound to ALDH2 and ALDH2*2 reveal how Alda-1 activates the wild-type enzyme and how it restores the activity of ALDH2*2 by acting as a structural chaperone.
1 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
2 Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, California, USA.
