Evidence map›Paper›PMID 14982931›Full record

ArticleThe Journal of biological chemistry2004

Biochemical, crystallographic, and mutagenic characterization of hint, the AMP-lysine hydrolase, with novel substrates and inhibitors.

Agnieszka Krakowiak, Helen C Pace, G Michael Blackburn, Martina Adams, Abdelaziz Mekhalfia, Renata Kaczmarek, Janina Baraniak, Wojciech J Stec, Charles Brenner

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.0field-weighted citation impact, top 15% 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

19 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Axonal neuropathy with neuromyotonia: there is a HINT.Brain : a journal of neurology · 2017
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. New autosomal recessive cerebellar ataxias with oculomotor apraxia.Current neurology and neuroscience reports · 2005
    Review
  16. Article
  17. Article
  18. Article
  19. 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 4 institutions in 3 countries.

Agnieszka KrakowiakStructural Biology and Bioinformatics Program, Kimmel Cancer Center, Philadelphia, Pennsylvania 19107, USA.
Helen C Pace
G Michael Blackburn
Martina Adams
Abdelaziz Mekhalfia
Renata Kaczmarek
Janina Baraniak
Wojciech J Stec
Charles Brenner
Sidney Kimmel Cancer Center · USUniversity of Sheffield · GBCentrum Badań Molekularnych i Makromolekularnych Polskiej Akademii Nauk · PLPolish Academy of Sciences · PL

Funding

Mechanism of Dnmt1 Up-regulation by Fhit LossR01CA075954 · NCI · UNIVERSITY OF IOWA · PI BRENNER, CHARLES M · 1997 to 2012
$3.0M
NCI NIH HHS CA75954NCI NIH HHS R01 CA075954
6 · The paper itself

Abstract

Hint, histidine triad nucleotide-binding protein, is a universally conserved enzyme that hydrolyzes AMP linked to lysine and, in yeast, functions as a positive regulator of the RNA polymerase II C-terminal domain kinase, Kin28. To explore the biochemical and structural bases for the adenosine phosphoramidate hydrolase activity of rabbit Hint, we synthesized novel substrates linking a p-nitroaniline group to adenylate (AMP-pNA) and inhibitors that consist of an adenosine group and 5'-sulfamoyl (AdoOSO(2)NH(2)) or N-ethylsulfamoyl (AdoOSO(2)NHCH(2)CH(3)) group. AMP-pNA is a suitable substrate for Hint that allowed characterization of the inhibitors; titration of each inhibitor into AMP-pNA assays revealed their K(i) values. The N-ethylsulfamoyl derivative has a 13-fold binding advantage over the sulfamoyl adenosine. The 1.8-A cocrystal structure of rabbit Hint with N-ethylsulfamoyl adenosine revealed a binding site for the ethyl group against Trp-123, a residue that reaches across the Hint dimer interface to interact with the alkyl portion of the inhibitor and, presumably, the alkyl portion of a lysyl substrate. Ser-107 is positioned to donate a hydrogen bond to the leaving group nitrogen. Consistent with a role in acid-base catalysis, the Hint S107A mutant protein displayed depressed catalytic activity.

Indexed as

Adenosine MonophosphateAmino Acid SubstitutionAnimalsBinding SitesCarrier ProteinsCrystallography, X-RayEnzyme InhibitorsHydrolasesKineticsRabbitsSubstrate Specificityadenosine 5'-phosphoramidate hydrolaseAdenosine MonophosphateCarrier ProteinsEnzyme Inhibitorshistidine triad nucleotide-binding protein, mammalsHydrolases

Identifiers

PMID14982931
PMCPMC2556070
OpenAlexW1973763289

What OpenQuestion holds

Textmetadata
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.