Dunn Ben M, Goodenow Maureen M, Gustchina Alla, Wlodawer Alexander
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
Genome Biol. 2002;3(4):REVIEWS3006. doi: 10.1186/gb-2002-3-4-reviews3006. Epub 2002 Mar 26.
The proteases of retroviruses, such as leukemia viruses, immunodeficiency viruses (including the human immunodeficiency virus, HIV), infectious anemia viruses, and mammary tumor viruses, form a family with the proteases encoded by several retrotransposons in Drosophila and yeast and endogenous viral sequences in primates. Retroviral proteases are key enzymes in viral propagation and are initially synthesized with other viral proteins as polyprotein precursors that are subsequently cleaved by the viral protease activity at specific sites to produce mature, functional units. Active retroviral proteases are homodimers, with each dimer structurally related to the larger class of single-chain aspartic peptidases. Each monomer has four structural elements: two distinct hairpin loops, a wide loop containing the catalytic aspartic acid and an alpha helix. Retroviral gene sequences can vary between infected individuals, and mutations affecting the binding cleft of the protease or the substrate cleavage sites can alter the response of the virus to therapeutic drugs. The need to develop new drugs against HIV will continue to be, to a large extent, the driving force behind further characterization of retroviral proteases.
逆转录病毒的蛋白酶，如白血病病毒、免疫缺陷病毒（包括人类免疫缺陷病毒HIV）、传染性贫血病毒和乳腺肿瘤病毒，与果蝇和酵母中的几种逆转座子以及灵长类动物中的内源性病毒序列所编码的蛋白酶构成一个家族。逆转录病毒蛋白酶是病毒繁殖中的关键酶，最初与其他病毒蛋白一起作为多蛋白前体合成，随后在特定位点被病毒蛋白酶活性切割，以产生成熟的功能单位。活性逆转录病毒蛋白酶是同二聚体，每个二聚体在结构上与更大的单链天冬氨酸肽酶类相关。每个单体有四个结构元件：两个不同的发夹环、一个包含催化天冬氨酸的宽环和一个α螺旋。逆转录病毒基因序列在受感染个体之间可能不同，影响蛋白酶结合裂隙或底物切割位点的突变可改变病毒对治疗药物的反应。在很大程度上，开发抗HIV新药的需求将继续成为进一步表征逆转录病毒蛋白酶的驱动力。
