Evidence map›Paper›PMID 10677347›Full record

ArticleThe Biochemical journal2000

HIV-2 protease is inactivated after oxidation at the dimer interface and activity can be partly restored with methionine sulphoxide reductase.

D A Davis, F M Newcomb, J Moskovitz, P T Wingfield, S J Stahl, J Kaufman, H M Fales, R L Levine, R Yarchoan

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in The Biochemical journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00006518 (Collection of Blood, Bone Marrow, Tumor, or Tissue Samples From Patients With HIV Infection, KSHV Infection, Viral-Related Pre-Malignant Lesions, and/or Cancer), which is not on this map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.4field-weighted citation impact, top 22% 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.

NCT00006518 recruitingnot on this map

Collection of Blood, Bone Marrow, Tumor, or Tissue Samples From Patients With HIV Infection, KSHV Infection, Viral-Related Pre-Malignant Lesions, and/or Cancer

TypeobservationalSponsorNational Cancer Institute (NCI)Ran2000Enrolled1,029ConditionsHIV, Kaposi's Sarcoma, Lymphomas, Multicentric Castleman's Disease
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
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

9 authors at 3 institutions in 1 country.

D A DavisHIV and AIDS Malignancy Branch, National Cancer Institute, 9000 Rockville Pike, National Institutes of Health, Bethesda, MD 20892-1906, USA. dadavis@helix.nih.gov
F M Newcomb
J Moskovitz
P T Wingfield
S J Stahl
J Kaufman
H M Fales
R L Levine
R Yarchoan
National Heart Lung and Blood Institute · USNational Institute of Arthritis and Musculoskeletal and Skin Diseases · USNational Institutes of Health · US

Funding

Oxidative Modification Of ProteinsZIAHL000225 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVINE, RODNEY L. · 2009 to 2025
$35.2M
Production Of HIV And HIV Related Proteins For Structural StudiesZIAAR041115 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI WINGFIELD, PAUL T · 2009 to 2025
$16.9M
OXIDATION OF PROTEINSZ01HL000225 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI LEVINE, RODNEY L. · 1985 to 2008
$4.2M
RECOMBINANT DNA PRODUCED HIV PROTEINS--PURIFICATION/STRUCTURAL CHARACTERZ01AR041115 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI WINGFIELD, PAUL T · 1996 to 2008
$889k
STRUCTURE OF NATURAL PRODUCTS USING INSTRUMENTAL METHODSZ01HL001003 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI FALES, HENRY M · 1985 to 2008
$875k
Analysis Of Peptides, Proteins, And Metabolites Using Mass SpectrometryZIAHL001003 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI FALES, HENRY · 2009 to 2010
$264k
6 · The paper itself

Abstract

Human immunodeficiency viruses encode a homodimeric protease that is essential for the production of infectious virus. Previous studies have shown that HIV-1 protease is susceptible to oxidative inactivation at the dimer interface at Cys-95, a process that can be reversed both chemically and enzymically. Here we demonstrate a related yet distinct mechanism of reversible inactivation of the HIV-2 protease. Exposure of the HIV-2 protease to H(2)O(2) resulted in conversion of the two methionine residues (Met-76 and Met-95) to methionine sulphoxide as determined by amino acid analysis and mass spectrometry. This oxidation completely inactivated protease activity. However, the activity could be restored (up to 40%) after exposure of the oxidized protease to methionine sulphoxide reductase. This treatment resulted in the reduction of methionine sulphoxide 95 but not methionine sulphoxide 76 to methionine, as determined by peptide mapping/mass spectrometry. We also found that exposure of immature HIV-2 particles to H(2)O(2) led to the inhibition of polyprotein processing in maturing virus particles comparable to that demonstrated for HIV-1 particles. Thus oxidative inactivation of the HIV protease in vitro and in maturing viral particles is not restricted to the type 1 proteases. These studies indicate that two distinct retroviral proteases are susceptible to inactivation after a very minor modification at residue 95 of the dimer interface and suggest that the dimer interface might be a viable target for the development of novel protease inhibitors.

Indexed as

Amino Acid SequenceAspartic Acid EndopeptidasesDimerizationEnzyme ActivationHIV-2HIV ProteaseHumansMethionine Sulfoxide ReductasesMolecular Sequence DataOxidation-ReductionOxidoreductasesSequence AlignmentVirus ReplicationAspartic Acid EndopeptidasesHIV Proteasemethionine sulfoxide reductaseMethionine Sulfoxide ReductasesOxidoreductasesp16 protease, Human immunodeficiency virus 2

Identifiers

PMID10677347
PMCPMC1220854
OpenAlexW2021773540

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.