据一篇发表于12月3日Nature杂志的研究报告，霍华德休斯医学研究所的研究人员在原子水平上对一种重要的酶——人亲环素A(human cyclophilin A)的内部结构进行研究，该酶可被HIV病毒用来实现自我复制。
这项研究首次结合了X-射线晶体学(x-ray crystallography)和核磁共振(nuclear magnetic resonance,NMR)技术，获得了该酶在具有催化效力的高能状态下蛋白质的内部结构图像。同时也揭示了这种结构如何影响该酶的催化效力。
在该报告中，研究人员还揭示了人亲环素A从少见的高能状态向常见的低能状态的相互转换(interconversion)过程。如果这种转换很快，那么酶的催化效率越高；反之亦然。
据研究人员Kern介绍，之前人们一直都认为通过催化底物可以加速化学反应的进程，但这项研究表明，蛋白质催化剂本身的活力也非常重要。（生物谷Bioon.com）
生物谷推荐原始出处：
Nature 462, 669-673 (3 December 2009) | doi:10.1038/nature08615
Hidden alternative structures of proline isomerase essential for catalysis
James S. Fraser1, Michael W. Clarkson2, Sheena C. Degnan1, Renske Erion1, Dorothee Kern2 & Tom Alber1
1 Department of Molecular and Cell Biology/QB3, University of California, Berkeley, California 94720-3220, USA
2 Department of Biochemistry, Howard Hughes Medical Institute, Brandeis University, Waltham, Massachusetts 02454, USA
3 Correspondence to: Dorothee Kern2Tom Alber1 Correspondence and requests for materials should be addressed to T.A. or D.K.
A long-standing challenge is to understand at the atomic level how protein dynamics contribute to enzyme catalysis. X-ray crystallography can provide snapshots of conformational substates sampled during enzymatic reactions1, while NMR relaxation methods reveal the rates of interconversion between substates and the corresponding relative populations1, 2. However, these current methods cannot simultaneously reveal the detailed atomic structures of the rare states and rationalize the finding that intrinsic motions in the free enzyme occur on a timescale similar to the catalytic turnover rate. Here we introduce dual strategies of ambient-temperature X-ray crystallographic data collection and automated electron-density sampling to structurally unravel interconverting substates of the human proline isomerase, cyclophilin A (CYPA, also known as PPIA). A conservative mutation outside the active site was designed to stabilize features of the previously hidden minor conformation. This mutation not only inverts the equilibrium between the substates, but also causes large, parallel reductions in the conformational interconversion rates and the catalytic rate. These studies introduce crystallographic approaches to define functional minor protein conformations and, in combination with NMR analysis of the enzyme dynamics in solution, show how collective motions directly contribute to the catalytic power of an enzyme.
