Evidence map›Paper›PMID 25416787›Full record

ArticleThe Journal of biological chemistry2015

Comparison of the enzymatic and functional properties of three cytosolic carboxypeptidase family members.

Hui-Yuan Wu, Yongqi Rong, Kristen Correia, Jaeki Min, James I Morgan

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
0.4field-weighted citation impact, top 35% 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

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. International journal of molecular sciences · 2022
    Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. 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

5 authors at 1 institution in 1 country.

Hui-Yuan WuFrom the Departments of Developmental Neurobiology and.
Yongqi RongFrom the Departments of Developmental Neurobiology and.
Kristen CorreiaFrom the Departments of Developmental Neurobiology and.
Jaeki MinChemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
James I MorganFrom the Departments of Developmental Neurobiology and jim.morgan@stjude.org.
St. Jude Children's Research Hospital · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
Function of Nna1 in Neuronal Death and Axon RegenerationR01NS051537 · NINDS · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI MORGAN, JAMES I · 2009 to 2013
$1.8M
NCI NIH HHS CA 21765NCI NIH HHS P30 CA021765NINDS NIH HHS NS051537NINDS NIH HHS R01 NS051537
6 · The paper itself

Abstract

Nna1 (CCP1) defines a subfamily of M14 metallocarboxypeptidases (CCP1-6) and is mutated in pcd (Purkinje cell degeneration) mice. Nna1, CCP4, and CCP6 are involved in the post-translational process of polyglutamylation, where they catalyze the removal of polyglutamate side chains. However, it is unknown whether these three cytosolic carboxypeptidases share identical enzymatic properties and redundant biological functions. We show that like Nna1, purified recombinant CCP4 and CCP6 deglutamylate tubulin, but unlike Nna1, neither rescues Purkinje cell degeneration in pcd mice, indicating that they do not have identical functions. Using biotin-based synthetic substrates, we established that the three enzymes are distinguishable based upon individual preferences for glutamate chain length, the amino acid immediately adjacent to the glutamate chain, and whether their activity is enhanced by nearby acidic amino acids. Nna1 and CCP4 remove the C-terminal glutamate from substrates with two or more glutamates, whereas CCP6 requires four or more glutamates. CCP4 behaves as a promiscuous glutamase, with little preference for chain length or neighboring amino acid composition. Besides glutamate chain length dependence, Nna1 and CCP6 exhibit higher k(cat)/K(m) when substrates contain nearby acidic amino acids. All cytosolic carboxypeptidases exhibit a monoglutamase activity when aspartic acid precedes a single glutamate, which, together with their other individual preferences for flanking amino acids, greatly increases the potential substrates for these enzymes and the biological processes in which they act. Additionally, Nna1 metabolized substrates mimicking the C terminus of tubulin in a way suggesting that the tyrosinated form of tubulin will accumulate in pcd mice.

Indexed as

Amino Acid SequenceAnimalsCarboxypeptidasesGTP-Binding ProteinsMiceMice, TransgenicNerve DegenerationPolyglutamic AcidPurkinje CellsSerine-Type D-Ala-D-Ala CarboxypeptidaseSubstrate SpecificityTubulinAgtpbp1 protein, mouseCarboxypeptidasesCCP4 protein, mouseCCP6 protein, mouseGTP-Binding ProteinsPolyglutamic AcidSerine-Type D-Ala-D-Ala CarboxypeptidaseTubulinCerebellumCytosolic CarboxypeptidaseEnzyme KineticsNeurodegenerationPolyglutamylationPost-translational Modification (PTM)Transgenic Mice

Identifiers

PMID25416787
PMCPMC4294487
OpenAlexW2049786488

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.