Saepuloh Uus, Iskandriati Diah, Pamungkas Joko, Solihin Dedy Duryadi, Mariya Sela Septima, Sajuthi Dondin
Primate Research Centre, Bogor Agricultural University (PSSP LPPM IPB), Jalan Lodaya II/5 Bogor 16151, Indonesia.
Faculty of Veterinary Medicine, Bogor Agricultural University, Kampus Darmaga, Bogor 16680, Indonesia.
Trop Life Sci Res. 2020 Oct;31(3):47-61. doi: 10.21315/tlsr2020.31.3.4. Epub 2020 Oct 15.
serotype-2 (SRV-2) is an important pathogenic agent in Asian macaques. It is a potential confounding variable in biomedical research. SRV-2 also provides a valuable viral model compared to other retroviruses which can be used for understanding many aspects of retroviral-host interactions and immunosuppression, infection mechanism, retroviral structure, antiretroviral and vaccine development. In this study, we isolated the gene encoding reverse transcriptase enzyme (RT) of SRV-2 that infected Indonesian cynomolgus monkey (Mf ET1006) and predicted the three dimensional structure model using the iterative threading assembly refinement (I-TASSER) computational programme. This SRV-2 RT Mf ET1006 consisted of 547 amino acids at nucleotide position 3284-4925 of whole genome SRV-2. The polymerase active site located in the finger/palm subdomain characterised by three conserved catalytic aspartates (Asp90, Asp165, Asp166), and has a highly conserved YDD motif as Tyr163, Met164, Asp165 and Asp166. We estimated that this SRV-2 RT Mf ET1006 structure has the accuracy of template modelling score (TM-score 0.90 ± 0.06) and root mean square deviation (RMSD) 4.7 ± 3.1Å, indicating that this model can be trusted and the accuracy can be seen from the appearance of protein folding in tertiary structure. The superpositionings between SRV-2 RT Mf ET1006 and Human Immunodeficiency Virus-1 (HIV-1) RT were performed to predict the structural in details and to optimise the best fits for illustrations. This SRV-2 RT Mf ET1006 structure model has the highest homology to HIV-1 RT (2B6A.pdb) with estimated accuracy at TM-score 0.911, RMSD 1.85 Å, and coverage of 0.953. This preliminary study of SRV-2 RT Mf ET1006 structure modelling is intriguing and provide some information to explore the molecular characteristic and biochemical mechanism of this enzyme.
2型猿猴泡沫病毒（SRV-2）是亚洲猕猴中的一种重要病原体。它是生物医学研究中一个潜在的混杂变量。与其他逆转录病毒相比，SRV-2还提供了一个有价值的病毒模型，可用于理解逆转录病毒与宿主相互作用和免疫抑制、感染机制、逆转录病毒结构、抗逆转录病毒药物及疫苗开发等诸多方面。在本研究中，我们分离了感染印度尼西亚食蟹猴（Mf ET1006）的SRV-2编码逆转录酶（RT）的基因，并使用迭代穿线组装优化（I-TASSER）计算程序预测了三维结构模型。该SRV-2 RT Mf ET1006由全基因组SRV-2核苷酸位置3284-4925处的547个氨基酸组成。聚合酶活性位点位于指状/掌状亚结构域，其特征为三个保守的催化天冬氨酸（Asp90、Asp165、Asp166），并且具有高度保守的YDD基序，即Tyr163、Met164、Asp165和Asp166。我们估计该SRV-2 RT Mf ET1006结构的模板建模得分（TM-score 0.90±0.06）和均方根偏差（RMSD）为4.7±3.1Å，表明该模型可信，且从三级结构中蛋白质折叠的外观可看出其准确性。对SRV-2 RT Mf ET1006和人类免疫缺陷病毒1型（HIV-1）RT进行了叠加，以详细预测结构并优化插图的最佳匹配。该SRV-2 RT Mf ET1006结构模型与HIV-1 RT（2B6A.pdb）具有最高同源性，估计准确性为TM-score 0.911、RMSD 1.85 Å和覆盖率0.953。对SRV-2 RT Mf ET1006结构建模的这项初步研究很有趣，并为探索该酶的分子特征和生化机制提供了一些信息。
