Nicholson L K, Yamazaki T, Torchia D A, Grzesiek S, Bax A, Stahl S J, Kaufman J D, Wingfield P T, Lam P Y, Jadhav P K
Molecular Structural Biology Unit, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nat Struct Biol. 1995 Apr;2(4):274-80. doi: 10.1038/nsb0495-274.
HIV protease is a homodimeric protein whose activity is essential to viral function. We have investigated the molecular dynamics of the HIV protease, thought to be important for proteinase function, bound to high affinity inhibitors using NMR techniques. Analysis of 15N spin relaxation parameters, of all but 13 backbone amide sites, reveals the presence of significant internal motions of the protein backbone. In particular, the flaps that cover the proteins active site of the protein have terminal loops that undergo large amplitude motions on the ps to ns time scale, while the tips of the flaps undergo a conformational exchange on the microsecond time scale. This enforces the idea that the flaps of the proteinase are flexible structures that facilitate function by permitting substrate access to and product release from the active site of the enzyme.
HIV蛋白酶是一种同二聚体蛋白，其活性对病毒功能至关重要。我们利用核磁共振技术研究了与高亲和力抑制剂结合的HIV蛋白酶的分子动力学，该动力学被认为对蛋白酶功能很重要。对除13个主链酰胺位点外的所有15N自旋弛豫参数进行分析，揭示了蛋白质主链存在显著的内部运动。特别是，覆盖该蛋白质活性位点的侧翼具有末端环，这些末端环在皮秒到纳秒的时间尺度上经历大幅度运动，而侧翼尖端在微秒时间尺度上发生构象交换。这强化了这样一种观点，即蛋白酶的侧翼是灵活的结构，通过允许底物进入酶的活性位点并从该位点释放产物来促进其功能。
