據(jù)一篇發(fā)表于12月3日Nature雜志的研究報告,，霍華德休斯醫(yī)學研究所的研究人員在原子水平上對一種重要的酶——人親環(huán)素A(human cyclophilin A)的內(nèi)部結(jié)構進行研究，該酶可被HIV病毒用來實現(xiàn)自我復制,。
這項研究首次結(jié)合了X-射線晶體學(x-ray crystallography)和核磁共振(nuclear magnetic resonance,NMR)技術，獲得了該酶在具有催化效力的高能狀態(tài)下蛋白質(zhì)的內(nèi)部結(jié)構圖像。同時也揭示了這種結(jié)構如何影響該酶的催化效力,。
在該報告中,，研究人員還揭示了人親環(huán)素A從少見的高能狀態(tài)向常見的低能狀態(tài)的相互轉(zhuǎn)換(interconversion)過程。如果這種轉(zhuǎn)換很快,，那么酶的催化效率越高,；反之亦然。
據(jù)研究人員Kern介紹,，之前人們一直都認為通過催化底物可以加速化學反應的進程,，但這項研究表明，蛋白質(zhì)催化劑本身的活力也非常重要,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
