變構(gòu)蛋白（別構(gòu)蛋白）是具有變構(gòu)劑行為的蛋白質(zhì),。蛋白質(zhì)分子空間結(jié)構(gòu)和其性質(zhì)及生理功能的關(guān)系也十分密切。此前一直認(rèn)為不同的蛋白質(zhì),，正因?yàn)榫哂胁煌目臻g結(jié)構(gòu),，因此具有不同的理化性質(zhì)和生理功能。效應(yīng)子分子被認(rèn)為通過與一個(gè)變構(gòu)點(diǎn)（與活性點(diǎn)明顯不同）結(jié)合,、從而誘導(dǎo)和穩(wěn)定蛋白的某一特定構(gòu)形狀態(tài)來控制變構(gòu)蛋白的活性,。
一項(xiàng)新的研究表明，認(rèn)為變構(gòu)蛋白的活性純粹由結(jié)構(gòu)調(diào)控的觀點(diǎn)應(yīng)當(dāng)予以修正,，將來自蛋白動(dòng)態(tài)的一個(gè)經(jīng)常占支配地位的貢獻(xiàn)包括進(jìn)去,。
Shiou-Ru Tzeng 和 Charalampos Kalodimos對(duì)與“降解物激活蛋白”（CAP）相結(jié)合的環(huán)AMP進(jìn)行了定性。CAP是被經(jīng)常用作變構(gòu)模型的一個(gè)轉(zhuǎn)錄激活蛋白,。他們出乎意料地發(fā)現(xiàn),，即便是當(dāng)處在一個(gè)從結(jié)構(gòu)上來講沒有活性的構(gòu)形時(shí)，CAP也能被蛋白動(dòng)態(tài)的變化所激活，以便與配體（DNA）結(jié)合,。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature 462, 368-372 (19 November 2009) | doi:10.1038/nature08560
Dynamic activation of an allosteric regulatory protein
Shiou-Ru Tzeng1,2 & Charalampos G. Kalodimos1,2
1 Department of Chemistry & Chemical Biology,
2 Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey 08854, USA
3 Correspondence to: Charalampos G. Kalodimos1,2 Correspondence and requests for materials should be addressed to C.G.K.
Allosteric regulation is used as a very efficient mechanism to control protein activity in most biological processes, including signal transduction, metabolism, catalysis and gene regulation1, 2, 3, 4, 5, 6. Allosteric proteins can exist in several conformational states with distinct binding or enzymatic activity. Effectors are considered to function in a purely structural manner by selectively stabilizing a specific conformational state, thereby regulating protein activity. Here we show that allosteric proteins can be regulated predominantly by changes in their structural dynamics. We have used NMR spectroscopy and isothermal titration calorimetry to characterize cyclic AMP (cAMP) binding to the catabolite activator protein (CAP), a transcriptional activator that has been a prototype for understanding effector-mediated allosteric control of protein activity7. cAMP switches CAP from the 'off' state (inactive), which binds DNA weakly and non-specifically, to the 'on' state (active), which binds DNA strongly and specifically. In contrast, cAMP binding to a single CAP mutant, CAP-S62F, fails to elicit the active conformation; yet, cAMP binding to CAP-S62F strongly activates the protein for DNA binding. NMR and thermodynamic analyses show that despite the fact that CAP-S62F-cAMP2 adopts the inactive conformation, its strong binding to DNA is driven by a large conformational entropy originating in enhanced protein motions induced by DNA binding. The results provide strong evidence that changes in protein motions may activate allosteric proteins that are otherwise structurally inactive.
