Wyttenbach Thomas, Liu Dengfeng, Bowers Michael T
Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, California 93106, USA.
J Am Chem Soc. 2008 May 7;130(18):5993-6000. doi: 10.1021/ja8002342. Epub 2008 Apr 8.
The interaction of the cyclic nonapeptide oxytocin (OT) with a number of alkaline earth and divalent transition metal ions (X(2+)) was examined employing mass spectrometry (MS) and ion mobility spectrometry (IMS) techniques in combination with molecular dynamics (MD) and density functional theory (DFT) calculations. Under acidic conditions it was found that OT exhibits an exceptionally strong affinity for all divalent metal ions resulting in strong OT + X peaks in the mass spectrum. Under basic conditions only Cu(2+) and Ni(2+)-OT complexes were detected and these were singly, doubly, triply, or quadruply deprotonated. Collision-induced dissociation of the OT - 3H + Cu complex yielded exclusively C-terminal Cu(2+)-containing fragments (Cu(2+)fragment(3-)), suggesting that the Cu(2+) ligation site includes deprotonated C-terminal backbone amide nitrogen atoms and the N-terminal amino nitrogen atom in OT - 3H + Cu. MD and DFT calculations indicate a square-planar complex is consistent with these observations and with experimental collision cross sections. MD and DFT calculations also indicate either an octahedral or trigonal-bipyramidal complex between Zn(2+) and OT is lowest in energy with carbonyl oxygens being the primary ligation sites. Both complexes yield cross sections in agreement with experiment. The biological impact of the structural changes induced in OT by divalent metal ion coodination is discussed.
采用质谱（MS）和离子淌度光谱（IMS）技术，并结合分子动力学（MD）和密度泛函理论（DFT）计算，研究了环状九肽催产素（OT）与多种碱土金属和二价过渡金属离子（X(2+)）之间的相互作用。发现在酸性条件下，OT对所有二价金属离子都表现出异常强的亲和力，导致质谱中出现强的OT + X峰。在碱性条件下，仅检测到Cu(2+)和Ni(2+)-OT络合物，且这些络合物发生了单质子化、双质子化、三质子化或四质子化。OT - 3H + Cu络合物的碰撞诱导解离仅产生含C端Cu(2+)的片段（Cu(2+)fragment(3-)），这表明在OT - 3H + Cu中，Cu(2+)的配位位点包括去质子化的C端主链酰胺氮原子和N端氨基氮原子。MD和DFT计算表明，平面正方形络合物与这些观察结果以及实验碰撞截面一致。MD和DFT计算还表明，Zn(2+)与OT之间的八面体或三角双锥络合物能量最低，羰基氧是主要的配位位点。两种络合物产生的截面均与实验结果一致。讨论了二价金属离子配位诱导OT结构变化的生物学影响。
