Weber I T
Crystallography Laboratory, NCI-Frederick Cancer Research Facility, Maryland 21701.
Proteins. 1990;7(2):172-84. doi: 10.1002/prot.340070206.
The model of human immunodeficiency virus (HIV-1) protease which was based on the crystal structure of Rous sarcoma virus (RSV) protease has been compared to the recently determined crystal structure of chemically synthesized HIV-1 protease. The overall difference between the model and crystal structure was 1.4 A root mean square (rms) deviation for 86 superimposed C alpha atoms. The position of the flexible flap differs in the model and six residues at the amino terminus were incorrectly placed. With these exceptions, all atoms of the model and crystal structure agree to 2.1 A rms deviation. The conformation of some surface bends in the model agrees less well with the crystal structure. Identical amino acids in RSV and HIV proteases were modeled more reliably than different types of amino acids. The amino acids which form the substrate binding site were modeled most accurately to 1.2 A rms deviation for all atoms compared to the crystal structure. This suggests that functionally significant regions of related proteins can be modeled with high accuracy. The model gave correct predictions for residues making interactions with the substrate, and therefore could be used to design inhibitors. The model based on the RSV protease structure is more similar to the experimental structure than are previous models based on the structures of non-viral aspartic proteases.
基于劳斯肉瘤病毒（RSV）蛋白酶晶体结构构建的人类免疫缺陷病毒（HIV-1）蛋白酶模型，已与最近测定的化学合成HIV-1蛋白酶晶体结构进行了比较。该模型与晶体结构之间的总体差异为86个叠加的Cα原子的均方根（rms）偏差1.4 Å。柔性瓣的位置在模型中有所不同，并且氨基末端的六个残基放置错误。除了这些例外，模型和晶体结构的所有原子在2.1 Å的均方根偏差内是一致的。模型中一些表面弯曲的构象与晶体结构的吻合度较低。RSV和HIV蛋白酶中相同的氨基酸比不同类型的氨基酸建模得更可靠。与晶体结构相比，形成底物结合位点的氨基酸对所有原子的建模最为准确，均方根偏差为1.2 Å。这表明相关蛋白质的功能重要区域可以高精度建模。该模型对与底物相互作用的残基做出了正确预测，因此可用于设计抑制剂。与基于非病毒天冬氨酸蛋白酶结构的先前模型相比，基于RSV蛋白酶结构的模型与实验结构更为相似。
