Akamine Pearl, Xuong Nguyen-Huu, Taylor Susan S
Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, California 92093-0654, USA.
Nat Struct Biol. 2002 Apr;9(4):273-7. doi: 10.1038/nsb780.
To understand the molecular mechanism underlying phosphoryl transfer of cAMP-dependent protein kinase, the structure of the catalytic subunit in complex with ADP, aluminum fluoride, Mg2+ ions and a substrate peptide was determined at 2.0 A resolution. Aluminum fluoride was modeled as AlF3 in a planar geometry; it is positioned 2.3 A from both the donor oxygen of ADP and the hydroxyl group of the recipient Ser residue. In this configuration, the aluminum atom forms a trigonal bipyramidal coordination with the oxygen atoms of the donor and recipient groups at the apical positions. This arrangement suggests that aluminum fluoride mimics the transition state and provides the first direct structural evidence for the in-line mechanism of phosphoryl transfer in a protein kinase.
为了解环磷酸腺苷依赖性蛋白激酶磷酸转移的分子机制，我们以2.0埃的分辨率确定了与ADP、氟化铝、Mg2+离子和底物肽形成复合物的催化亚基的结构。氟化铝被模拟为平面几何结构的AlF3；它距离ADP的供体氧原子和受体丝氨酸残基的羟基均为2.3埃。在这种构型中，铝原子与处于顶端位置的供体和受体基团的氧原子形成三角双锥配位。这种排列表明氟化铝模拟了过渡态，并为蛋白激酶中磷酸转移的线性机制提供了首个直接的结构证据。
