Evidence map›Paper›PMID 20695887›Full record

ArticleThe FEBS journal2010

Amprenavir complexes with HIV-1 protease and its drug-resistant mutants altering hydrophobic clusters.

Chen-Hsiang Shen, Yuan-Fang Wang, Andrey Y Kovalevsky, Robert W Harrison, Irene T Weber

Open access · bronzeAbstract readComparative Study
In one paragraph

Article in The FEBS journal, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

67 citing papers in PubMed, 131 citations in OpenAlex.

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  6. Enthalpic Classification of Water Molecules in Target-Ligand Binding.Journal of chemical information and modeling · 2024
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  13. Article
  14. Article
  15. Article
  16. Elasticity-Associated Functionality and Inhibition of the HIV Protease.Advances in experimental medicine and biology · 2022
    Article
  17. Therapeutic potential of HIV-1 entry inhibitor peptidomimetics.Experimental biology and medicine (Maywood, N.J.) · 2021
    Review
  18. Article
  19. Article
  20. Article

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Chen-Hsiang ShenDepartment of Biology, Molecular Basis of Disease Program, Georgia State University, Atlanta, GA, USA.
Yuan-Fang Wang
Andrey Y Kovalevsky
Robert W Harrison
Irene T Weber
Georgia State University · US

Funding

ACTIVITY OF RESISTANT VARIANTS OF HIV PROTEASER01GM062920 · NIGMS · GEORGIA STATE UNIVERSITY · PI WEBER, IRENE T · 2000 to 2012
$3.3M
Inhibition of Resistant Variants of HIV ProteaseU01GM062920 · NIGMS · GEORGIA STATE UNIVERSITY · PI HARRISON, ROBERT WILSON, WEBER, IRENE T · 2013 to 2018
$2.1M
NIGMS NIH HHS GM062920NIGMS NIH HHS R01 GM062920NIGMS NIH HHS U01 GM062920
6 · The paper itself

Abstract

The structural and kinetic effects of amprenavir (APV), a clinical HIV protease (PR) inhibitor, were analyzed with wild-type enzyme and mutants with single substitutions of V32I, I50V, I54V, I54M, I84V and L90M that are common in drug resistance. Crystal structures of the APV complexes at resolutions of 1.02-1.85 Å reveal the structural changes due to the mutations. Substitution of the larger side chains in PR(V32I) , PR(I54M) and PR(L90M) resulted in the formation of new hydrophobic contacts with flap residues, residues 79 and 80, and Asp25, respectively. Mutation to smaller side chains eliminated hydrophobic interactions in the PR(I50V) and PR(I54V) structures. The PR(I84V)-APV complex had lost hydrophobic contacts with APV, the PR(V32I)-APV complex showed increased hydrophobic contacts within the hydrophobic cluster and the PR(I50V) complex had weaker polar and hydrophobic interactions with APV. The observed structural changes in PR(I84V)-APV, PR(V32I)-APV and PR(I50V)-APV were related to their reduced inhibition by APV of six-, 10- and 30-fold, respectively, relative to wild-type PR. The APV complexes were compared with the corresponding saquinavir complexes. The PR dimers had distinct rearrangements of the flaps and 80's loops that adapt to the different P1' groups of the inhibitors, while maintaining contacts within the hydrophobic cluster. These small changes in the loops and weak internal interactions produce the different patterns of resistant mutations for the two drugs.

Indexed as

MutationAmino Acid SubstitutionCarbamatesCrystallography, X-RayDimerizationDrug Resistance, Multiple, ViralFuransHIV-1HIV ProteaseHIV Protease InhibitorsHydrophobic and Hydrophilic InteractionsKineticsMolecular ConformationProtein BindingProtein Interaction Domains and MotifsSaquinaviramprenavirCarbamatesFuransHIV ProteaseHIV Protease Inhibitorsp16 protease, Human immunodeficiency virus 1SaquinavirSulfonamides

Identifiers

PMID20695887
PMCPMC2975871
OpenAlexW2161531618

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.