Effect of substrate residues on the P2′ preference of retroviral proteinases
Effect of substrate residues on the P2′ preference of retroviral proteinases
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DOI：
10.1046/j.1432-1327.1999.00687.x
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发表时间：
1999-09-01
期刊：
影响因子：
--
通讯作者：
Tözsér, J
中科院分区：
文献类型：
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作者：
Boross, P;Bagossi, P;Tözsér, J
研究了基质蛋白/衣壳蛋白（MA/CA）和CA/p2切割位点序列对HIV-1蛋白酶优先选择P2 ' Glu残基的底物序列要求。这些序列分别代表典型的1型（-芳香族 *Pro-）和2型（-疏水性 * 疏水性-）切割位点序列。虽然在1型序列背景下，发现P2 ' Glu优于Ile或Gln强烈依赖于离子强度和底物的P2-P2 '区域外部的残基，但当典型的1型底物序列残基被置换到外部区域中时，其在2型底物中保持优选。特异性常数的pH曲线表明，在两种序列背景下，与具有不带电残基的底物相比，具有P2 ' Glu的底物的最佳pH值较低。在包括马传染性贫血病毒（EIAV）和鼠白血病病毒（MuLV）在内的各种逆转录病毒的天然存在的逆转录病毒切割位点中，P2 ' Glu的频率非常低，这表明这种残基在逆转录病毒生命周期中可能不具有一般调节作用。事实上，与HN-I和HIV-2不同，EIAV和MuLV蛋白酶在MA/CA或CA/p2序列环境中不支持P2 ' Glu。
The substrate sequence requirements for preference toward P2 ' Glu residue by human immunodeficiency virus type 1 (HIV-l) proteinase were studied in both the matrix protein/ capsid protein (MA/CA) and CA/p2 cleavage site sequence contexts. These sequences represent typical type 1 (-aromatic*Pro-) and type 2 (-hydrophobic* hydrophobic-) cleavage site sequences, respectively. While in the type 1 sequence context, the preference for P2 ' Glu over Ile or Gin was found to be strongly dependent on the ionic strength and the residues being outside the P2-P2 ' region of the substrate, it remained preferable in the type 2 substrates when typical type 1 substrate sequence residues were substituted into the outside regions. The pH profile of the specificity constants suggested a lower pH optimum for substrates having P2 ' Glu in contrast to those having uncharged residues, in both sequence contexts. The very low frequency of P2 ' Glu in naturally occurring retroviral cleavage sites of various retroviruses including equine infectious anemia virus (EIAV) and murine leukemia virus (MuLV) suggests that such a residue may not have a general regulatory role in the retroviral life cycle. In fact, unlike HN-I and HIV-2, EIAV and MuLV proteinases do not favor P2 ' Glu in either the MA/CA or CA/p2 sequence contexts.