Locations of Anti-AIDS Drug Binding Sites and Resistance Mutations in the Three-dimensional Structure of HIV-1 Reverse Transcriptase

1994 ◽  
Vol 243 (3) ◽  
pp. 369-387 ◽  
Author(s):  
Chris Tantillo ◽  
Jianping Ding ◽  
Alfredo Jacobo-Molina ◽  
Raymond G. Nanni ◽  
Paul L. Boyer ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Binding Sites ◽  
Three Dimensional ◽  
Drug Binding ◽  
Dimensional Structure ◽  
Resistance Mutations ◽  
Three Dimensional Structure ◽  
Drug Binding Sites ◽  
Hiv 1

scholarly journals A novel protein descriptor for the prediction of drug binding sites

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Mingjian Jiang ◽  
Zhen Li ◽  
Yujie Bian ◽  
Zhiqiang Wei
Keyword(s):  
Binding Site ◽  
Binding Sites ◽  
Three Dimensional ◽  
Drug Binding ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Site Prediction ◽  
Drug Binding Sites ◽  
Protein Descriptor ◽  
Novel Protein

Abstract Background Binding sites are the pockets of proteins that can bind drugs; the discovery of these pockets is a critical step in drug design. With the help of computers, protein pockets prediction can save manpower and financial resources. Results In this paper, a novel protein descriptor for the prediction of binding sites is proposed. Information on non-bonded interactions in the three-dimensional structure of a protein is captured by a combination of geometry-based and energy-based methods. Moreover, due to the rapid development of deep learning, all binding features are extracted to generate three-dimensional grids that are fed into a convolution neural network. Two datasets were introduced into the experiment. The sc-PDB dataset was used for descriptor extraction and binding site prediction, and the PDBbind dataset was used only for testing and verification of the generalization of the method. The comparison with previous methods shows that the proposed descriptor is effective in predicting the binding sites. Conclusions A new protein descriptor is proposed for the prediction of the drug binding sites of proteins. This method combines the three-dimensional structure of a protein and non-bonded interactions with small molecules to involve important factors influencing the formation of binding site. Analysis of the experiments indicates that the descriptor is robust for site prediction.

scholarly journals Construction of A Preliminary Three-Dimensional Structure Simian betaretrovirus Serotype-2 (SRV-2) Reverse Transcriptase Isolated from Indonesian Cynomolgus Monkey

2020 ◽  
Vol 31 (3) ◽  
pp. 47-61
Author(s):  
Uus Saepuloh ◽  
Diah Iskandriati ◽  
Joko Pamungkas ◽  
Dedy Duryadi Solihin ◽  
Sela Septima Mariya ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Cynomolgus Monkey ◽  
Tertiary Structure ◽  
Vaccine Development ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Nucleotide Position ◽  
Structure Model ◽  
Three Dimensional Structure ◽  
Hiv 1

Simian betaretrovirus 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 YMDD 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.

Three-dimensional structure of the RNase H domain of HIV-1 reverse transcriptase at 2. 4 Å resolution

Peptides ◽  
1992 ◽  
pp. 682-684
Author(s):  
David A. Matthews ◽  
Jay F. Davies ◽  
Zuzana Hostomska ◽  
Zdenek Hostomsky ◽  
Steven R. Jordan
Keyword(s):  
Reverse Transcriptase ◽  
Three Dimensional ◽  
Rnase H ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Hiv 1

scholarly journals Mapping Mutations in Proteins of SARS CoV-2 Indian Isolates on to the Three-Dimensional Structures

2020 ◽  
Author(s):  
Kunchur Guruprasad
Keyword(s):  
Rna Polymerase ◽  
Binding Sites ◽  
Three Dimensional ◽  
Data Bank ◽  
Drug Binding ◽  
Dimensional Structure ◽  
Rna Dependent Rna Polymerase ◽  
Indian Isolates ◽  
Drug Binding Sites ◽  
Structural Insights

<p>The amino acid residue mutations observed in SARS CoV-2 RNA dependent RNA polymerase, helicase, endoRNAse and spike proteins from Indian isolates, relative to the reference SARS CoV-2 proteins from the Wuhan Hu-1 isolate, were mapped onto the protein three-dimensional structure templates available in the Protein Data Bank.<b> </b>The secondary structure conformations corresponding to the mutations, their locations and proximity to functionally important residues in these proteins and to the drug binding sites in RNA dependent RNA polymerase and endoRNAse targets were analysed. Our analyses provide structural insights into the mutations in these SARS CoV-2 proteins.</p>

Review of HIV-1 reverse transcriptase three-dimensional structure: Implications for drug design

1993 ◽  
Vol 1 (1) ◽  
pp. 129-150 ◽  
Author(s):  
Raymond G. Nanni ◽  
Jianping Ding ◽  
Alfredo Jacobo-Molina ◽  
Stephen H. Hughes ◽  
Edward Arnold
Keyword(s):  
Drug Design ◽  
Reverse Transcriptase ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Hiv 1

scholarly journals Mapping Mutations in Proteins of SARS CoV-2 Indian Isolates on to the Three-Dimensional Structures

2020 ◽  
Author(s):  
Kunchur Guruprasad
Keyword(s):  
Rna Polymerase ◽  
Binding Sites ◽  
Three Dimensional ◽  
Data Bank ◽  
Drug Binding ◽  
Dimensional Structure ◽  
Rna Dependent Rna Polymerase ◽  
Indian Isolates ◽  
Drug Binding Sites ◽  
Structural Insights

<p>The amino acid residue mutations observed in SARS CoV-2 RNA dependent RNA polymerase, helicase, endoRNAse and spike proteins from Indian isolates, relative to the reference SARS CoV-2 proteins from the Wuhan Hu-1 isolate, were mapped onto the protein three-dimensional structure templates available in the Protein Data Bank.<b> </b>The secondary structure conformations corresponding to the mutations, their locations and proximity to functionally important residues in these proteins and to the drug binding sites in RNA dependent RNA polymerase and endoRNAse targets were analysed. Our analyses provide structural insights into the mutations in these SARS CoV-2 proteins.</p>

Three-dimensional Structure and Evolution of HIV-1 Protease

1990 ◽  
pp. 79-91
Author(s):  
Andrew Wilderspin ◽  
Duncan Gaskin ◽  
Risto Lapatto ◽  
Tom Blundell ◽  
Andrew Hemmings ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Hiv 1

scholarly journals Efficacy of Dideoxynucleosides against Human Foamy Virus and Relationship to Its Reverse Transcriptase Amino Acid Sequence and Structure

2001 ◽  
Vol 75 (15) ◽  
pp. 7184-7187 ◽  
Author(s):  
Anne Yvon-Groussin ◽  
Pierre Mugnier ◽  
Philippe Bertin ◽  
Marc Grandadam ◽  
Henri Agut ◽  
...  
Keyword(s):  
Amino Acid ◽  
Reverse Transcriptase ◽  
Foamy Virus ◽  
Three Dimensional ◽  
Retroviral Vectors ◽  
Dimensional Structure ◽  
Human Foamy Virus ◽  
Amino Acid Residues ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Human foamy virus (HFV), a retrovirus of simian origin which occasionally infects humans, is the basis of retroviral vectors in development for gene therapy. Clinical considerations of how to treat patients developing an uncontrolled infection by either HFV or HFV-based vectors need to be raised. We determined the susceptibility of the HFV to dideoxynucleosides and found that only zidovudine was equally efficient against the replication of human immunodeficiency virus type 1 (HIV-1) and HFV. By contrast, zalcitabine (ddC), lamivudine (3TC), stavudine (d4T), and didanosine (ddI) were 3-, 3-, 30-, and 46-fold less efficient against HFV than against HIV-1, respectively. Some amino acid residues known to be involved in HIV-1 resistance to ddC, 3TC, d4T, and ddI were found at homologous positions of HFV reverse transcriptase (RT). These critical amino acids are located at the same positions in the three-dimensional structure of HIV-1 and HFV RT, suggesting that both enzymes share common patterns of inhibition.

Three-dimensional structure of aspartyl protease from human immunodeficiency virus HIV-1

Nature ◽  
1989 ◽  
Vol 337 (6208) ◽  
pp. 615-620 ◽  
Author(s):  
Manuel A. Navia ◽  
Paula M. D. Fitzgerald ◽  
Brian M. McKeever ◽  
Chih-Tai Leu ◽  
Jill C. Heimbach ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Aspartyl Protease ◽  
Three Dimensional Structure ◽  
Immunodeficiency Virus ◽  
Hiv 1
Sign in / Sign up

Export Citation Format

Share Document