Yamanishi Mamoru, Vlasie Monica, Banerjee Ruma
Biochemistry Department, University of Nebraska, Lincoln, NE 68588-0664, USA.
Trends Biochem Sci. 2005 Jun;30(6):304-8. doi: 10.1016/j.tibs.2005.04.008.
Many organic cofactors are both rare and reactive. They are usually in low abundance, which poses problems for efficient collision-based targeting to dependent enzymes, whereas their reactivity is problematic for side reactions. Sequestration and escorted delivery presents one solution to this conundrum, but such porters, if they exist, are mostly unknown. In humans, the mitochondrial enzyme methylmalonyl-coenzyme A mutase uses coenzyme B(12) (adenosylcobalamin) but would be inactive if bound to the cofactor precursor that is delivered to the mitochondrion. Adenosyltransferase converts cob(II)alamin to coenzyme B(12). Based on kinetic evidence for interaction between the two enzymes, the 40-fold greater affinity for coenzyme B(12) and the higher coordination number for cobalt in the mutase, we propose that the adenosyltransferase is a dual-function protein: an enzyme that synthesizes coenzyme B(12) and a chaperone that delivers it.
许多有机辅助因子既稀有又具有反应活性。它们通常含量很低，这给基于碰撞的高效靶向依赖酶带来了问题，而它们的反应活性又会引发副反应。隔离和护送递送为这一难题提供了一种解决方案，但这类搬运蛋白（如果存在的话）大多尚不为人所知。在人类中，线粒体酶甲基丙二酰辅酶A变位酶使用辅酶B12（腺苷钴胺素），但如果与输送到线粒体的辅因子前体结合则会失去活性。腺苷转移酶将钴胺素（II）转化为辅酶B12。基于两种酶之间相互作用的动力学证据、对辅酶B12高40倍的亲和力以及变位酶中钴的高配位数，我们提出腺苷转移酶是一种双功能蛋白：一种合成辅酶B12的酶和一种递送它的伴侣蛋白。
