Modeling and docking studies on novel mutants (K71L and T204V) of the ATPase domain of human heat shock 70 kDa protein 1.
Modeling and docking studies on novel mutants (K71L and T204V) of the ATPase domain of human heat shock 70 kDa protein 1.
复制标题
DOI：
10.3390/ijms15046797
复制
发表时间：
2014-04-22
影响因子：
5.6
通讯作者：
Hamdan S
中科院分区：
文献类型：
--
作者：
Elengoe A;Naser MA;Hamdan S
探索人腺病毒和热休克蛋白70之间的蛋白质相互作用的目的是利用潜在的协同相互作用来增强抗肿瘤功效并降低癌症治疗中的毒性。然而，Hsp 70与人腺病毒血清型5的E1 A32 kDa的蛋白质相互作用仍有待阐明。本研究对人热休克蛋白70 kDa 1（PDB：1 HJO）的ATP酶结构域的两个残基进行了突变。然后使用PyMol软件构建3D突变体模型（K71 L和T204 V）。通过PROSINS、ProQ、ERRAT、Verify 3D和ProSA模块对结构进行评价。所有证据表明，所有蛋白质模型都是可接受的，质量良好。从UniProt（P03255）检索E1 A32 kDa基序，并使用Autodock 4.2程序与NBD、K71 L和T204 V进行对接相互作用。最佳的最低结合能值为-9.09 kcal/mol，被选为新型T204 V。此外，通过RMSD、RMSF、氢键和盐桥分析验证了蛋白质-配体复合物的结构。这表明T204 V-E1 A32 kDa基序复合物在所有三种复合物结构中最稳定。本研究提供了有关热休克蛋白70与E1 A32 kDa基序之间相互作用的信息，强调了未来设计合理的癌症治疗药物和疫苗的前景。
The purpose of exploring protein interactions between human adenovirus and heat shock protein 70 is to exploit a potentially synergistic interaction to enhance anti-tumoral efficacy and decrease toxicity in cancer treatment. However, the protein interaction of Hsp70 with E1A32 kDa of human adenovirus serotype 5 remains to be elucidated. In this study, two residues of ATPase domain of human heat shock 70 kDa protein 1 (PDB: 1 HJO) were mutated. 3D mutant models (K71L and T204V) using PyMol software were then constructed. The structures were evaluated by PROCHECK, ProQ, ERRAT, Verify 3D and ProSA modules. All evidence suggests that all protein models are acceptable and of good quality. The E1A32 kDa motif was retrieved from UniProt (P03255), as well as subjected to docking interaction with NBD, K71L and T204V, using the Autodock 4.2 program. The best lowest binding energy value of −9.09 kcal/mol was selected for novel T204V. Moreover, the protein-ligand complex structures were validated by RMSD, RMSF, hydrogen bonds and salt bridge analysis. This revealed that the T204V-E1A32 kDa motif complex was the most stable among all three complex structures. This study provides information about the interaction between Hsp70 and the E1A32 kDa motif, which emphasizes future perspectives to design rational drugs and vaccines in cancer therapy.
登录
查看更多内容
影响因子：
3.7
作者：
Doss CG;Nagasundaram N
通讯作者：
Nagasundaram N
影响因子：
8
作者：
COLOVOS, C;YEATES, TO
通讯作者：
YEATES, TO
影响因子：
1.8
作者：
Kuntal BK;Aparoy P;Reddanna P
通讯作者：
Reddanna P
影响因子：
10.5
作者：
Campbell, KS;Mullane, KP;DeCaprio, JA
通讯作者：
DeCaprio, JA
影响因子：
64.8
作者：
Glotzer, JB;Saltik, M;Cotten, M
通讯作者：
Cotten, M