Evidence map›Paper›PMID 21213249›Full record

ArticleProtein science : a publication of the Protein Society2011

Measuring rapid hydrogen exchange in the homodimeric 36 kDa HIV-1 integrase catalytic core domain.

Nicholas C Fitzkee, Dennis A Torchia, Ad Bax

Erratum issuedAbstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
–field-weighted citation impact
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

24 citing papers in PubMed.

  1. Article
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  15. Mechanisms of amyloid formation revealed by solution NMR.Progress in nuclear magnetic resonance spectroscopy · 2015
    Review
  16. Article
  17. Visualizing transient dark states by NMR spectroscopy.Quarterly reviews of biophysics · 2015
    Article
  18. Article
  19. Article
  20. Measuring hydrogen exchange rates in invisible protein excited states.Proceedings of the National Academy of Sciences of the United States of America · 2014
    Article
4 · The record

Corrections and comments

  • Erratum issued
5 · Who and what money

Authors and funding

3 authors.

Nicholas C FitzkeeLaboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0520, USA.
Dennis A Torchia
Ad Bax

Funding

study of the HIV integrase catalytic core domain and inhibitor bindingZIADK075024 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI BAX, AD · 2009 to 2012
$973k
Intramural NIH HHS
6 · The paper itself

Abstract

Measurements of rapid hydrogen exchange (HX) of water with protein amide sites contain valuable information on protein structure and function, but current NMR methods for measuring HX rates are limited in their applicability to large protein systems. An alternate method for measuring rapid HX is presented that is well-suited for larger proteins, and we apply the method to the deuterated, homodimeric 36 kDa HIV-1 integrase catalytic core domain (CCD). Using long mixing times for water-amide magnetization exchange at multiple pH values, HX rates spanning more than four orders of magnitude were measured, as well as NOE cross-relaxation rates to nearby exchangeable protons. HX protection factors for the CCD are found to be large (>10(4)) for residues along the dimer interface, but much smaller in many other regions. Notably, the catalytic helix (residues 152-167) exhibits low HX protection at both ends, indicative of fraying at both termini as opposed to just the N-terminal end, as originally thought. Residues in the LEDGF/p75 binding pocket also show marginal stability, with protection factors in the 10-100 range (∼1.4-2.7 kcal/mol). Additionally, elevated NOE cross-relaxation rates are identified and, as expected, correspond to proximity of the amide proton to a rapidly exchanging proton, typically from an OH side chain. Indirect NOE transfer between H(2) O and the amide proton of I141, a residue in the partially disordered active site of the enzyme, suggests its proximity to the side chain of S147, an interaction seen in the DNA-bound form for a homologous integrase.

Indexed as

Catalytic DomainProtein Structure, TertiaryHIV IntegraseHumansHydrogenModels, MolecularNuclear Magnetic Resonance, BiomolecularHIV IntegraseHydrogenp31 integrase protein, Human immunodeficiency virus 1

Identifiers

PMID21213249
PMCPMC3064830

What OpenQuestion holds

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Registered trials

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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.