Processing protease and reverse transcriptase from human immunodeficiency virus type I polyprotein in Escherichia coli

Mous, Jan; Heimer, Edgar P.; Grice, S F Le

doi:10.1128/jvi.62.4.1433-1436.1988

Cited by 143 publications

(35 citation statements)

References 14 publications

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“…For example, in the structures of RSV PR and the almost identical avian myeloblastosis associated virus (MAV) PR, there is a helical turn in this region that is not present in HIV-1 PR. Mous et al 35 reported that peptide antibodies were raised against the HIV-1 PR sequence in the range of residues 18-40. It may be suggested that such different surface structural features in different retroviral PRs can serve as an epitope for interactions with antibodies.…”

Section: Hydrophobic Interior Residuesmentioning

confidence: 99%

Comparative analysis of the sequences and structures of HIV‐1 and HIV‐2 proteases

1991

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The different isolates available for HIV-1 and HIV-2 were compared for the region of the protease (PR) sequence, and the variations in amino acids were analyzed with respect to the crystal structure of HIV-1 PR with inhibitor. Based on the extensive homology (39 identical out of 99 residues), models were built of the HIV-2 PR complexed with two different aspartic protease inhibitors, acetylpepstatin and a renin inhibitor, H-261. Comparison of the HIV-1 PR crystal structure and the HIV-2 PR model structure and the analysis of the changes found in different isolates showed that correlated substitutions occur in the hydrophobic interior of the molecule and at surface residues involved in ionic or hydrogen bond interactions. The substrate binding residues of HIV-1 and HIV-2 PRs show conservative substitutions of four residues. The difference in affinity of HIV-1 and HIV-2 PRs for the two inhibitors appears to be due in part to the change of Val 32 in HIV-1 PR to Ile in HIV-2 PR.

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Section: Hydrophobic Interior Residuesmentioning

confidence: 99%

Comparative analysis of the sequences and structures of HIV‐1 and HIV‐2 proteases

1991

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“…2, 3b), although the conformation of this loop is predicted quite well. The modeling of this loop was aided by the good Table I1 and averaged for a) residues identical in RSV and HIV-1 PR sequences, b) functionally similar amino acid types (VIIIL; SIT; DINiEIQ occur), c) different types of amino acids, and d) residues forming the substrate binding site (8,9,(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)76, 80-84, and 87). Then there is an analysis by type of amino acid segregated into e) polar sidechain in either RSV or HIV PR sequence, and f ) hydrophobic side chain in both RSV and HIV PR sequences.…”

Section: Comparison By Amino Acid Typementioning

confidence: 99%

Evaluation of homology modeling of HIV Protease

Weber¹

1990

Proteins

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The model of human immunodeficiency virus (HIV-1) protease which was based on the crystal structure of Rous sarcoma virus (RSV) protease has been compared to the recently determined crystal structure of chemically synthesized HIV-1 protease. The overall difference between the model and crystal structure was 1.4 A root mean square (rms) deviation for 86 superimposed C alpha atoms. The position of the flexible flap differs in the model and six residues at the amino terminus were incorrectly placed. With these exceptions, all atoms of the model and crystal structure agree to 2.1 A rms deviation. The conformation of some surface bends in the model agrees less well with the crystal structure. Identical amino acids in RSV and HIV proteases were modeled more reliably than different types of amino acids. The amino acids which form the substrate binding site were modeled most accurately to 1.2 A rms deviation for all atoms compared to the crystal structure. This suggests that functionally significant regions of related proteins can be modeled with high accuracy. The model gave correct predictions for residues making interactions with the substrate, and therefore could be used to design inhibitors. The model based on the RSV protease structure is more similar to the experimental structure than are previous models based on the structures of non-viral aspartic proteases.

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“…In contrast with the NRTIs and NNRTIs, which were all discovered using cell-based assays, the PIs were rationally designed based on insight into the molecular mode of action of an aspartyl protease [57], and determination of their inhibitory potency in enzymatic assays. Recombinant DNA technology offered the best source to clone, express and purify the HIV protease [58,59], thus allowing the testing of potential inhibitors. Following the peptidomimetic lead, the hydroxyethylamine transition-state mimetic was clearly the best of those considered, leading first to the discovery of saquinavir [55] soon to be followed by indinavir, ritonavir and the other peptidomimetic HIV protease inhibitors [60][61][62][63].…”

Section: Protease Inhibitors (Pis)mentioning

confidence: 99%

The history of antiretrovirals: key discoveries over the past 25 years

Clercq

2009

Reviews in Medical Virology

160

100

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Within 25 years after zidovudine (3'-azido-2',3'-dideoxythymidine, AZT) was first described as an inhibitor of HIV replication, 25 anti-HIV drugs have been formally approved for clinical use in the treatment of HIV infections: seven nucleoside reverse transcriptase inhibitors (NRTIs): zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine; one nucleotide reverse transcriptase inhibitor (NtRTI): tenofovir [in its oral prodrug form: tenofovir disoproxil fumarate (TDF)]; four non-nucleoside reverse transcriptase inhibitors (NNRTIs): nevirapine, delavirdine, efavirenz and etravirine; ten protease inhibitors (PIs): saquinavir, ritonavir, indinavir, nelfinavir, amprenavir, lopinavir, atazanavir, fosamprenavir, tipranavir and darunavir; one fusion inhibitor (FI): enfuvirtide; one co-receptor inhibitor (CRI): maraviroc and one integrase inhibitor (INI): raltegravir. These compounds are used in various drug combination (some at fixed dose) regimens so as to achieve the highest possible benefit and tolerability, and to diminish the risk of virus-drug resistance development.

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Processing protease and reverse transcriptase from human immunodeficiency virus type I polyprotein in Escherichia coli

Cited by 143 publications

References 14 publications

Comparative analysis of the sequences and structures of HIV‐1 and HIV‐2 proteases

Comparative analysis of the sequences and structures of HIV‐1 and HIV‐2 proteases

Evaluation of homology modeling of HIV Protease

The history of antiretrovirals: key discoveries over the past 25 years

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