美國印第安那大學(xué)和斯坦福大學(xué)的醫(yī)學(xué)院的研究人員發(fā)現(xiàn)了一類新的“化學(xué)分子伴侶(chemical chaperone)”,，這種物質(zhì)能夠恢復(fù)某些發(fā)生突變的酶的功能。該研究發(fā)表在1月10日的Nature Structural & Molecular Biology雜志上，在該報告中,，他們描述了這種化學(xué)物質(zhì)如何在機體中發(fā)揮作用的過程,，這項發(fā)現(xiàn)或有助于開發(fā)新的藥物,，治療因心臟病發(fā)作引起的肌肉損傷,。
這項研究由印第安納大學(xué)Thomas Hurley博士主持，研究發(fā)現(xiàn),，一種命名為Alda-1的化學(xué)物質(zhì)能夠修復(fù)發(fā)生突變的ALDH2酶的功能,。ALDH2酶對酒精代謝或因心臟病發(fā)作缺氧所產(chǎn)生的毒素的代謝有重要作用,。
但是在一些人群(如40%的亞洲裔人群)中，ALDH2酶是以一種突變體的形式存在于機體中,。攜帶突變體ALDH2酶的人群其患心血管損傷的風險比正常人更大,。（生物谷Bioon.com）
該研究組曾在2008年Science雜志上報道，Alda-1可繞過機體一般的信號系統(tǒng)直接激活A(yù)LDH2酶,，從而降低心肌組織損傷,。在最近的這項研究報告中，描述了Alda-1如何激活A(yù)LDH2酶的過程,。研究人員將這個過程比喻成一個“木工工藝”過程,，Alda-1的作用類似于一個楔子，可以結(jié)合到ALDH2酶的一個關(guān)鍵位點,，從而使酶恢復(fù)正常功能,。詳情見：Science ：心臟的損傷控制
生物谷推薦原始出處：
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.
